Background:Numerous academic studies have explored the utilization of pharmacogenomics in the context of immunologic diseases in recent years.Despite this,there is a notable absence of scientometric analyses focusing ...Background:Numerous academic studies have explored the utilization of pharmacogenomics in the context of immunologic diseases in recent years.Despite this,there is a notable absence of scientometric analyses focusing on the literature within this domain.Methods:This study employs bibliometric methods to systematically categorize the literature pertaining to pharmacogenomics in the context of immune diseases,with the aim of identifying research trends,key areas of interest,and prominent research institutions in this field.Results:Scientometric analysis compared 812 international publications with 71 Chinese publications,finding that the prevailing international research focus is on the precise dosing and therapy of immunosuppressants like mercaptopurine,a topic more extensively explored than in Chinese literature.Conclusion:It is found that the research focus is centered on precision medication and therapy,with a particular emphasis on the utilization of different immunosuppressants like mercaptopurine and tacrolimus.Furthermore,it is anticipated that precision dosing of emerging immunosuppressants like sirolimus will be a significant are a of future research.展开更多
Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxi...Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.展开更多
The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transpla...The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient's immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians. DATA SOURCES:The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors. RESULTS:Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly-used im- munosuppressants. Recent progress in study of pharmaco-kinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM). CONCLUSIONS:Individualizing organ recipient's immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.展开更多
Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more c...Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.展开更多
In 2003,two newguidelines for hyperten—sive prevention andmanagement have beenprovided by AmericanJNC7 and European So-ciety of Hypertension.They advocated that thephysician should choosedrugs following individ—uali...In 2003,two newguidelines for hyperten—sive prevention andmanagement have beenprovided by AmericanJNC7 and European So-ciety of Hypertension.They advocated that thephysician should choosedrugs following individ—ualized treatment,展开更多
BACKGROUND Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment.Pharmacogenomics can help guide individualized drug therapy and improve outcomes.CASE SUMMARY...BACKGROUND Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment.Pharmacogenomics can help guide individualized drug therapy and improve outcomes.CASE SUMMARY We report a case of a preterm infant with multiple complications,including bronchopulmonary dysplasia(BPD),sepsis,intracranial hemorrhage,and hypertension.The infant was treated with various drugs,including dexamethasone and amlodipine.The infant was diagnosed with neonatal hypertension based on blood pressure measurements exceeding the 95th percentile for his age and sex.The possible causes of hypertension included dexamethasone,hydrochlorothiazide,spironolactone,and BPD.The infant was treated with oral amlodipine to lower his blood pressure.A pharmacogenomic test was performed to evaluate the genetic polymorphisms of ABCB1 and CYP3A5,which are involved in the metabolism and transport of dexamethasone and amlodipine.The infant’s blood pressure was well controlled after the dose of amlodipine was reduced according to the pharmacogenomic results.The infant had a stable general condition and was discharged on the 100th d after birth.CONCLUSION This case illustrates the importance of regular blood pressure monitoring and etiological investigation in preterm infants with hypertension.Pharmacogenomics can provide useful information for individualized drug therapy and safety in this population.展开更多
Natural products have been implemented in medicine through use as herbal medications, chemical compound extraction for prescription medication, or a natural source of food to fight various infections and diseases. Gen...Natural products have been implemented in medicine through use as herbal medications, chemical compound extraction for prescription medication, or a natural source of food to fight various infections and diseases. Genetics has played a role in identifying various interactions between existing drugs and side effects. In addition, various food allergies have been identified with children in recent years, suggesting genetic associations between certain populations carrying specific genetic alleles. The recent availability of genomic data and our increased understanding of the effects of genetic variations permit a quantitative examination of the contribution of genetic variation to efficacy or toxicity of compounds derived from natural sources. The identification of target molecules relevant for diseases allows screening for natural products capable of inhibiting targets which can lead to the development of rational treatment of various diseases including neurobiological disorders, cancer, osteoporosis, and cardiovascular diseases. This allows for more opportunities to predict the response of individual patients. Identification of genetic variations that arose as a consequence of naturally occurring compounds will help identify gene alleles, or protein ligands that can affect the pharmacodynamic and pharmacokinetics of the natural products in question. In addition, diet modification and precautions to food products can be identified to help consumers limit or increase certain food intake. Understanding the molecular mechanisms underlying these interactions and their modification by genetic variation is expected to result in the development of new drugs that optimize individual health. We expect that strategies for individualized therapies will lead to improved results for patients.展开更多
Pharmacogenetics refers to the effect of single nucleotide polymorphisms(SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving ...Pharmacogenetics refers to the effect of single nucleotide polymorphisms(SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction(HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus(HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1(MDR1) 3435 C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity.展开更多
The availability of newer technologies for identification and characterization of the human genome has enabled our understanding of the genetic variations in a majority of human diseases.Human genomic sequence varies ...The availability of newer technologies for identification and characterization of the human genome has enabled our understanding of the genetic variations in a majority of human diseases.Human genomic sequence varies in less than 1%among the different population group and these differences known as gene polymorphisms are the primary reasons for differences in individuals’response to various drug therapy.Also understanding the genetic changes may enable implementation of targeted therapy,thus providing for effective treatment strategies and minimizing the adverse side effects.Pharmacogenomics is a recent development in the field of personalized medicine which focuses on the genetic determinants of drug response at the levels of entire human genome.It primarily deals with tailoring of drug therapy for every individual based on their genetic make-up and identifying new target in various diseases for drug therapy.While the application of pharmacogenomics in systemic illness is well researched,its role in oral diseases needs documentation.Identifying specific targets in periodontitis,head and neck cancer,infections and genetic disorders can be beneficial in discovery of new drugs.This editorial provides an overview of basics of pharmacoge-nomics,its current role in disease management and its potential role in various head and neck diseases.展开更多
BACKGROUND Pharmacogenomics(PG)testing is under-utilised in Australia.Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their...BACKGROUND Pharmacogenomics(PG)testing is under-utilised in Australia.Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their care,with the aim to inform wider adoption of PG into routine clinical practice.AIM To investigate the frequency of actionable drug gene interactions and assess the perceived utility of PG among patients and clinicians.METHODS We conducted a retrospective audit of PG undertaken by 100 patients at an Australian public hospital genetics service from 2018 to 2021.Via electronic surveys we compared and contrasted the experience,understanding and usage of results between these patients and their clinicians.RESULTS Of 100 patients who had PG,84% were taking prescription medications,of which 67% were taking medications with actionable drug-gene interactions.Twenty-five out of 81 invited patients and 17 out of 89 invited clinicians completed the surveys.Sixty-eight percent of patients understood their PG results and 48% had medications changed following testing.Paired patient-clinician surveys showed patient-perceived utility and experience was positive,contrasting their clinicians’hesitancy on PG adoption who identified insufficient education/training,lack of clinical support,test turnaround time and cost as barriers to adoption.CONCLUSION Our dichotomous findings between the perspectives of our patient and clinician cohorts suggest the uptake of PG is likely to be driven by patients and clinicians need to be prepared to provide information and guidance to their patients.展开更多
With the aging of society, dementia has become a more and more serious social problem. Alzhei-mer’s disease （AD） is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is t...With the aging of society, dementia has become a more and more serious social problem. Alzhei-mer’s disease （AD） is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is the main drug currently in symptomatic treatment. How-ever,the effcacy of donepezil was moderate, with the patient variably responding to the treatment with donepe-zil. The commonest adverse events in the treatment were nausea,vomiting,and diarrhea; QT prolongation rarely occurred. Many patients gave up treatment because of adverseevents orlack of effcacy. Pharmacogenomicsis developed on the basis of pharmacogenetics, by studying the polymorphisms in genes involved in drug metabolicenzymes, transporter and drug receptor, to guide individ-ualized treatment. In terms of the pharmacogenomics on the effcacyof onepezil, there is no clear conclusion ex-cept CYP2D6 genotype affecting drug clearance.展开更多
Osteoporosis has emerged as a significant health issue among postmenopausal women.Addressing this concern necessitates a multifaceted approach encompassing genetics,pharmacogenomics,bone turnover markers,lifestyle fac...Osteoporosis has emerged as a significant health issue among postmenopausal women.Addressing this concern necessitates a multifaceted approach encompassing genetics,pharmacogenomics,bone turnover markers,lifestyle factors,concurrent medical conditions,biomarkers,and advanced imaging techniques.Nonetheless,challenges in terms of cost-effectiveness and ethical considerations do exist.Fortunately,the convergence of technological progress and research endeavors offers a promising trajectory.The integration of genetic testing and pharmacogenomics into clinical practice holds substantial potential.This integration empowers healthcare professionals to forecast treatment responses and pinpoint individuals with elevated susceptibility,thereby enabling the implementation of tailored and efficacious interventions that optimize outcomes–personalized medicine.Given the intricate nature of osteoporosis,personalized strategies stand to greatly benefit women grappling with this condition.Further research and collaborative efforts are imperative to propel advancements within this domain,paving the way for further breakthroughs.展开更多
Background:Precision medicine(PM)has taken center stage in healthcare since the completion of the genomic project.Developed countries have gradually integrated PM into mainstream patient management.However,Nigeria sti...Background:Precision medicine(PM)has taken center stage in healthcare since the completion of the genomic project.Developed countries have gradually integrated PM into mainstream patient management.However,Nigeria still grapples with wide acceptance,key translational research and implementation of PM.This study sought to explore the knowledge and attitude of PM among pharmacists as key stakeholders in the healthcare team.Methods:A cross‐sectional study was conducted in selected tertiary hospitals across the country.A 21‐item semi‐structured questionnaire was administered by hybrid online and physical methods and the results analyzed with Statistical Package for the Social Sciences Version 25.Descriptive statistics were used to summarize the data.A chi‐square test was employed to determine the association of knowledge of PM and the sociodemographic characteristics of the study population.Results:A total of 167 hospital pharmacists participated in the study.A high proportion of the participants are familiar with artificial intelligence(91.75%),Pharmacogenomics(84.5%),and precision medicine(61%).Overall,38.9%of the pharmacists had a good knowledge while 13.2%had a poor knowledge of PM and associated terms.The level of knowledge did not correlate significantly with gender(X^(2)=3.21,p=0.201),age(X^(2)=5,p=0.27),marital status(X^(2)=3.21,p=0.201),and professional level(X^(2)=6.85,p=0.144).The most important value of precision medicine to hospital pharmacists is the ability to minimize the impact of disease through preventive medicine(49%)while a large portion are pursuing and or actively planning to pursue additional education in precision medicine.Conclusions:There is a highly positive attitude toward the prospect of PM among hospital pharmacists in Nigeria.Education modules in this field are highly recommended as most do not have a holistic knowledge of terms used in PM.Also,more research aimed at translating PM knowledge into clinical practice is recommended.展开更多
This study addressed the critical need for an integrated,personalized approach to perimenopausal mental health,addressing both biological and psychosocial fac-tors.Current research highlighted the influence of hormona...This study addressed the critical need for an integrated,personalized approach to perimenopausal mental health,addressing both biological and psychosocial fac-tors.Current research highlighted the influence of hormonal fluctuations,genetic predispositions,and lifestyle factors in shaping perimenopausal mental health outcomes.This transitional period is marked by significant hormonal fluctuations contributing to heightened anxiety,depression,and sleep disturbances,affecting the women’s quality of life.Traditional pharmacological treatments,including selective serotonin reuptake inhibitors and hormone replacement therapy,have limitations due to variable efficacy and side effects,emphasizing the need for precision medicine.Advancements in pharmacogenomics and metabolomics provide new avenues for individualized treatments,with genetic markers(e.g.,Solute carrier organic anion transporter family member 1B1,estrogen receptor 1/estrogen receptor 2,and tachykinin receptor 3)guiding hormone therapy resp-onses.Emerging digital health technologies,such as artificial intelligence-driven diagnostics,wearable monitoring,and telehealth platforms,offer scalable,real-time mental health support,though regulatory and clinical validation challenges remain.Furthermore,integrative treatment models combining hormone-based therapy with non-pharmacological interventions demonstrate significant efficacy in alleviating perimenopausal symptoms.Future directions should prioritize the clinical validation and ethical implementation of digital health solutions,ensuring safety,efficacy,and user accessibility.A multidisciplinary,patient-centric model,incorporating genetics,endocrinology,digital health,and psychosocial interventions,is essential for optimizing perimenopausal mental health outcomes.展开更多
Founder events influence recessive diseases in highly endogamous populations.Several Indian populations have experienced significant founder events due to strict endogamy.However,the clinical implications of it remain...Founder events influence recessive diseases in highly endogamous populations.Several Indian populations have experienced significant founder events due to strict endogamy.However,the clinical implications of it remain underexplored.Therefore,we perform whole-exome sequencing of 281 individuals from four South Indian populations,characterized by high IBD scores.Our study reveals a high inbreeding rate of 59%across the populations.We identify∼29.2%of the variants that are exclusively present in a single population and uncover 1284 unreported exonic variants,underscoring the underrepresentation of Indian populations in global databases.Among these,23 are predicted to be deleterious,all of which are present in a heterozygous state;they may be pathogenic when homozygous,an expected phenomenon in endogamous populations.Approximately 16%-33%of the identified pathogenic variants showed significantly higher occurrence rates compared with the South Asian populations from 1000 Genomes dataset.Pharmacogenomic analysis revealed distinct allele frequencies of variants in CYP450 and non-CYP450 genes,highlighting heterogeneous drug responses and associated risks.We report a high prevalence of ankylosing spondylitis in Reddy population,linked to the HLA-B∗27:04 allele and strong founder effect.Our findings highlight the need for extensive genomic research in understudied Indian populations for a better understanding of disease risk and evolving strategies for precision and preventive medicine.展开更多
Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical ...Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.展开更多
The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision med- icine, pharmacogenomics, the study...The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision med- icine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual＇s particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pbarmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.展开更多
Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, t...Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase(TKI), anaplastic lymphoma kinase(ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s).Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.展开更多
Pediatric acute lymphoblastic leukemia(ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenan...Pediatric acute lymphoblastic leukemia(ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine(6-MP) and methotrexate(MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment.6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase(TPMT), nudix hydrolase 15(NUDT15), and potentially inosine triphosphatase(ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1(SLCO1B1) and dihydrofolate reductase(DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1(SLC19A1)and thymidylate synthetase(TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.展开更多
Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor ge...Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor.This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors(TKIs),which terrifically revolutionized the prognosis of GIST patients.Currently,it is well established that tumor mutational status is the main player in clinical outcome;however,with the research advances,it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes.For this reason,in the era of tailored/personalized medicine,each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.展开更多
基金the National Key Research and Development Program of China(2021YFC2702005)Beijing Hospitals Authority’s Ascent Plan(DFL20221001)+1 种基金R&D Program of Beijing Municipal Education Commission(KZ202210025030)Beijing Municipal Hospital Scientific Research and Cultivation Program(PX2023043).
文摘Background:Numerous academic studies have explored the utilization of pharmacogenomics in the context of immunologic diseases in recent years.Despite this,there is a notable absence of scientometric analyses focusing on the literature within this domain.Methods:This study employs bibliometric methods to systematically categorize the literature pertaining to pharmacogenomics in the context of immune diseases,with the aim of identifying research trends,key areas of interest,and prominent research institutions in this field.Results:Scientometric analysis compared 812 international publications with 71 Chinese publications,finding that the prevailing international research focus is on the precise dosing and therapy of immunosuppressants like mercaptopurine,a topic more extensively explored than in Chinese literature.Conclusion:It is found that the research focus is centered on precision medication and therapy,with a particular emphasis on the utilization of different immunosuppressants like mercaptopurine and tacrolimus.Furthermore,it is anticipated that precision dosing of emerging immunosuppressants like sirolimus will be a significant are a of future research.
文摘Interindividual differences in the toxicity and response to anticancer therapies are currently observed in practically all available treatment regimens. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available drug therapy according the genetic profile. Several mechanisms have been suggested to contribute to chemo-therapeutic drug resistance: amplification or overexpression of membrane transporters, changes in cellular proteins involved in detoxification or in DNA repair, apoptosis and activation of oncogenes or tumor suppressor genes. Colorectal cancer (CRC) is regarded as intrinsically resistant to chemotherapy. Several molecular markers predictive of CRC therapy have been included during the last decade but their results in different studies complicate their application in practical clinical. The simultaneous testing of multiple markers predictive of response could help to identify more accurately the true role of these polymorphisms in CRC therapy. This review analyzes the role of genetic variants in genes involved in the action mechanisms of the drugs used at present in colorectal cancer.
文摘The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient's immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians. DATA SOURCES:The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors. RESULTS:Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly-used im- munosuppressants. Recent progress in study of pharmaco-kinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM). CONCLUSIONS:Individualizing organ recipient's immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.
文摘Pharmacogenetics and pharmacogenomics deal with the role of genetic factors in drug effectiveness and adverse drug reactions. The promise of a personalized medicine is beginning to be explored but requires much more clinical and translational research. Specific DNA abnormalities in some cancers already have led to effective targeted treatments. Racially determined frequency differences in pharmacogenetic traits may affect choice of treatment requiring specific testing rather than basing treatments according to racial designation. The role of genes in variable responses to foreign chemicals (xenobiotics) has been termed ecogenetics or toxicogenetics raising problems in public health and occupational medicine. Nutrigenetics refers to genetic variation in response to nutrients and may affect nutritional requirements and predisposition to chronic disease.
文摘In 2003,two newguidelines for hyperten—sive prevention andmanagement have beenprovided by AmericanJNC7 and European So-ciety of Hypertension.They advocated that thephysician should choosedrugs following individ—ualized treatment,
文摘BACKGROUND Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment.Pharmacogenomics can help guide individualized drug therapy and improve outcomes.CASE SUMMARY We report a case of a preterm infant with multiple complications,including bronchopulmonary dysplasia(BPD),sepsis,intracranial hemorrhage,and hypertension.The infant was treated with various drugs,including dexamethasone and amlodipine.The infant was diagnosed with neonatal hypertension based on blood pressure measurements exceeding the 95th percentile for his age and sex.The possible causes of hypertension included dexamethasone,hydrochlorothiazide,spironolactone,and BPD.The infant was treated with oral amlodipine to lower his blood pressure.A pharmacogenomic test was performed to evaluate the genetic polymorphisms of ABCB1 and CYP3A5,which are involved in the metabolism and transport of dexamethasone and amlodipine.The infant’s blood pressure was well controlled after the dose of amlodipine was reduced according to the pharmacogenomic results.The infant had a stable general condition and was discharged on the 100th d after birth.CONCLUSION This case illustrates the importance of regular blood pressure monitoring and etiological investigation in preterm infants with hypertension.Pharmacogenomics can provide useful information for individualized drug therapy and safety in this population.
文摘Natural products have been implemented in medicine through use as herbal medications, chemical compound extraction for prescription medication, or a natural source of food to fight various infections and diseases. Genetics has played a role in identifying various interactions between existing drugs and side effects. In addition, various food allergies have been identified with children in recent years, suggesting genetic associations between certain populations carrying specific genetic alleles. The recent availability of genomic data and our increased understanding of the effects of genetic variations permit a quantitative examination of the contribution of genetic variation to efficacy or toxicity of compounds derived from natural sources. The identification of target molecules relevant for diseases allows screening for natural products capable of inhibiting targets which can lead to the development of rational treatment of various diseases including neurobiological disorders, cancer, osteoporosis, and cardiovascular diseases. This allows for more opportunities to predict the response of individual patients. Identification of genetic variations that arose as a consequence of naturally occurring compounds will help identify gene alleles, or protein ligands that can affect the pharmacodynamic and pharmacokinetics of the natural products in question. In addition, diet modification and precautions to food products can be identified to help consumers limit or increase certain food intake. Understanding the molecular mechanisms underlying these interactions and their modification by genetic variation is expected to result in the development of new drugs that optimize individual health. We expect that strategies for individualized therapies will lead to improved results for patients.
文摘Pharmacogenetics refers to the effect of single nucleotide polymorphisms(SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction(HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus(HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1(MDR1) 3435 C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity.
文摘The availability of newer technologies for identification and characterization of the human genome has enabled our understanding of the genetic variations in a majority of human diseases.Human genomic sequence varies in less than 1%among the different population group and these differences known as gene polymorphisms are the primary reasons for differences in individuals’response to various drug therapy.Also understanding the genetic changes may enable implementation of targeted therapy,thus providing for effective treatment strategies and minimizing the adverse side effects.Pharmacogenomics is a recent development in the field of personalized medicine which focuses on the genetic determinants of drug response at the levels of entire human genome.It primarily deals with tailoring of drug therapy for every individual based on their genetic make-up and identifying new target in various diseases for drug therapy.While the application of pharmacogenomics in systemic illness is well researched,its role in oral diseases needs documentation.Identifying specific targets in periodontitis,head and neck cancer,infections and genetic disorders can be beneficial in discovery of new drugs.This editorial provides an overview of basics of pharmacoge-nomics,its current role in disease management and its potential role in various head and neck diseases.
基金Supported by Partially funded by St Vincent’s Health Australia Inclusive Health ProgramEarly Career Research Grant from Avant.
文摘BACKGROUND Pharmacogenomics(PG)testing is under-utilised in Australia.Our research provides Australia-specific data on the perspectives of patients who have had PG testing and those of the clinicians involved in their care,with the aim to inform wider adoption of PG into routine clinical practice.AIM To investigate the frequency of actionable drug gene interactions and assess the perceived utility of PG among patients and clinicians.METHODS We conducted a retrospective audit of PG undertaken by 100 patients at an Australian public hospital genetics service from 2018 to 2021.Via electronic surveys we compared and contrasted the experience,understanding and usage of results between these patients and their clinicians.RESULTS Of 100 patients who had PG,84% were taking prescription medications,of which 67% were taking medications with actionable drug-gene interactions.Twenty-five out of 81 invited patients and 17 out of 89 invited clinicians completed the surveys.Sixty-eight percent of patients understood their PG results and 48% had medications changed following testing.Paired patient-clinician surveys showed patient-perceived utility and experience was positive,contrasting their clinicians’hesitancy on PG adoption who identified insufficient education/training,lack of clinical support,test turnaround time and cost as barriers to adoption.CONCLUSION Our dichotomous findings between the perspectives of our patient and clinician cohorts suggest the uptake of PG is likely to be driven by patients and clinicians need to be prepared to provide information and guidance to their patients.
文摘With the aging of society, dementia has become a more and more serious social problem. Alzhei-mer’s disease （AD） is a major cause of dementia, and there is no drug to reverse the disease progression. Donepezil is the main drug currently in symptomatic treatment. How-ever,the effcacy of donepezil was moderate, with the patient variably responding to the treatment with donepe-zil. The commonest adverse events in the treatment were nausea,vomiting,and diarrhea; QT prolongation rarely occurred. Many patients gave up treatment because of adverseevents orlack of effcacy. Pharmacogenomicsis developed on the basis of pharmacogenetics, by studying the polymorphisms in genes involved in drug metabolicenzymes, transporter and drug receptor, to guide individ-ualized treatment. In terms of the pharmacogenomics on the effcacyof onepezil, there is no clear conclusion ex-cept CYP2D6 genotype affecting drug clearance.
文摘Osteoporosis has emerged as a significant health issue among postmenopausal women.Addressing this concern necessitates a multifaceted approach encompassing genetics,pharmacogenomics,bone turnover markers,lifestyle factors,concurrent medical conditions,biomarkers,and advanced imaging techniques.Nonetheless,challenges in terms of cost-effectiveness and ethical considerations do exist.Fortunately,the convergence of technological progress and research endeavors offers a promising trajectory.The integration of genetic testing and pharmacogenomics into clinical practice holds substantial potential.This integration empowers healthcare professionals to forecast treatment responses and pinpoint individuals with elevated susceptibility,thereby enabling the implementation of tailored and efficacious interventions that optimize outcomes–personalized medicine.Given the intricate nature of osteoporosis,personalized strategies stand to greatly benefit women grappling with this condition.Further research and collaborative efforts are imperative to propel advancements within this domain,paving the way for further breakthroughs.
文摘Background:Precision medicine(PM)has taken center stage in healthcare since the completion of the genomic project.Developed countries have gradually integrated PM into mainstream patient management.However,Nigeria still grapples with wide acceptance,key translational research and implementation of PM.This study sought to explore the knowledge and attitude of PM among pharmacists as key stakeholders in the healthcare team.Methods:A cross‐sectional study was conducted in selected tertiary hospitals across the country.A 21‐item semi‐structured questionnaire was administered by hybrid online and physical methods and the results analyzed with Statistical Package for the Social Sciences Version 25.Descriptive statistics were used to summarize the data.A chi‐square test was employed to determine the association of knowledge of PM and the sociodemographic characteristics of the study population.Results:A total of 167 hospital pharmacists participated in the study.A high proportion of the participants are familiar with artificial intelligence(91.75%),Pharmacogenomics(84.5%),and precision medicine(61%).Overall,38.9%of the pharmacists had a good knowledge while 13.2%had a poor knowledge of PM and associated terms.The level of knowledge did not correlate significantly with gender(X^(2)=3.21,p=0.201),age(X^(2)=5,p=0.27),marital status(X^(2)=3.21,p=0.201),and professional level(X^(2)=6.85,p=0.144).The most important value of precision medicine to hospital pharmacists is the ability to minimize the impact of disease through preventive medicine(49%)while a large portion are pursuing and or actively planning to pursue additional education in precision medicine.Conclusions:There is a highly positive attitude toward the prospect of PM among hospital pharmacists in Nigeria.Education modules in this field are highly recommended as most do not have a holistic knowledge of terms used in PM.Also,more research aimed at translating PM knowledge into clinical practice is recommended.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.RS-2023-00237287。
文摘This study addressed the critical need for an integrated,personalized approach to perimenopausal mental health,addressing both biological and psychosocial fac-tors.Current research highlighted the influence of hormonal fluctuations,genetic predispositions,and lifestyle factors in shaping perimenopausal mental health outcomes.This transitional period is marked by significant hormonal fluctuations contributing to heightened anxiety,depression,and sleep disturbances,affecting the women’s quality of life.Traditional pharmacological treatments,including selective serotonin reuptake inhibitors and hormone replacement therapy,have limitations due to variable efficacy and side effects,emphasizing the need for precision medicine.Advancements in pharmacogenomics and metabolomics provide new avenues for individualized treatments,with genetic markers(e.g.,Solute carrier organic anion transporter family member 1B1,estrogen receptor 1/estrogen receptor 2,and tachykinin receptor 3)guiding hormone therapy resp-onses.Emerging digital health technologies,such as artificial intelligence-driven diagnostics,wearable monitoring,and telehealth platforms,offer scalable,real-time mental health support,though regulatory and clinical validation challenges remain.Furthermore,integrative treatment models combining hormone-based therapy with non-pharmacological interventions demonstrate significant efficacy in alleviating perimenopausal symptoms.Future directions should prioritize the clinical validation and ethical implementation of digital health solutions,ensuring safety,efficacy,and user accessibility.A multidisciplinary,patient-centric model,incorporating genetics,endocrinology,digital health,and psychosocial interventions,is essential for optimizing perimenopausal mental health outcomes.
基金supported by the DBT JRF-SRF research fellowship.KT was supported the J C Bose Fellowship from Science and Engineering Research Board(SERB),Department of Science and Technology,Government of India(JCB/2019/000027)CSIR Bhatnagar Fellowship,from Council of Scientific and Industrial Research(CSiR),Ministry of Science and Technology,Government of India.
文摘Founder events influence recessive diseases in highly endogamous populations.Several Indian populations have experienced significant founder events due to strict endogamy.However,the clinical implications of it remain underexplored.Therefore,we perform whole-exome sequencing of 281 individuals from four South Indian populations,characterized by high IBD scores.Our study reveals a high inbreeding rate of 59%across the populations.We identify∼29.2%of the variants that are exclusively present in a single population and uncover 1284 unreported exonic variants,underscoring the underrepresentation of Indian populations in global databases.Among these,23 are predicted to be deleterious,all of which are present in a heterozygous state;they may be pathogenic when homozygous,an expected phenomenon in endogamous populations.Approximately 16%-33%of the identified pathogenic variants showed significantly higher occurrence rates compared with the South Asian populations from 1000 Genomes dataset.Pharmacogenomic analysis revealed distinct allele frequencies of variants in CYP450 and non-CYP450 genes,highlighting heterogeneous drug responses and associated risks.We report a high prevalence of ankylosing spondylitis in Reddy population,linked to the HLA-B∗27:04 allele and strong founder effect.Our findings highlight the need for extensive genomic research in understudied Indian populations for a better understanding of disease risk and evolving strategies for precision and preventive medicine.
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.
基金supported by the Major National R&D Projects (Grant No.2012ZX09506001-004)National Natural Science Foundation of China (Grant No.81273578)
文摘The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. As a fundamental element in precision med- icine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individual＇s particular drug response. In this article, we review the contributions of genetic polymorphisms to major individual variations in drug pharmacotherapy, focusing specifically on the pbarmacogenomics of phase-I drug metabolizing enzymes and transporters. Substantial frequency differences in key variants of drug metabolizing enzymes and transporters, as well as their possible functional consequences, have also been discussed across geographic regions. The current effort illustrates the common presence of variability in drug responses among individuals and across all geographic regions. This information will aid health-care professionals in prescribing the most appropriate treatment aimed at achieving the best possible beneficial outcomes while avoiding unwanted effects for a particular patient.
文摘Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase(TKI), anaplastic lymphoma kinase(ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s).Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.
基金supports from the NIH/NIGMS (Grant Nos. U01GM61393 and K08GM089941)NIH/NCI (Grant No. R21 CA139278)+2 种基金Avon Foundation Research Grant, University of Chicago Cancer Center Support Grant (Grant No. P30 CA14599)Breast Cancer SPORE Career Development Award (Grant No. CA125183)the National Center for Advancing Translational Sciences of the NIH (Grant No. UL1RR024999) of the United States
文摘Pediatric acute lymphoblastic leukemia(ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine(6-MP) and methotrexate(MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment.6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase(TPMT), nudix hydrolase 15(NUDT15), and potentially inosine triphosphatase(ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1(SLCO1B1) and dihydrofolate reductase(DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1(SLC19A1)and thymidylate synthetase(TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.
文摘Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor.This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors(TKIs),which terrifically revolutionized the prognosis of GIST patients.Currently,it is well established that tumor mutational status is the main player in clinical outcome;however,with the research advances,it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes.For this reason,in the era of tailored/personalized medicine,each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.
