BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric ac...BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.展开更多
BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of ...BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of epilepsy.However,very few studies have investigated the relevance of genetic variations in epilepsy and anti-epileptic drug resistance.AIM To investigate associations between polymorphisms,rs121917953 T/A and rs121918623 C/T,and drug resistance in epilepsy patients in the north Indian population.METHODS A total of 100 age-and sex-matched epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and SCN1A rs121918623 C/T*and rs121917953 T/A*polymorphisms were analyzed by the allele specific-PCR technique.χ^(2)and Fisher’s exact test were used to estimate differences between the distribution of SCN1A rs121918623 and rs121917953 gene polymorphisms among various groups.The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.RESULTS For the SCN1A rs121917953 T/A*(D188V)polymorphism,a significantly higher proportion of individuals with AT genotype were observed in the drug-resistant group as compared to the drug-responsive group.Additionally,a higher risk association was exhibited by AT genotype for drug resistance with an odds ratio of 3.51 and P value=0.017.For the SCN1A rs121918623 C/T*(T875M)polymorphism,no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.CONCLUSION Our findings indicate that the SCN1A polymorphism D188V is associated with a higher risk of drug resistance for the AT variant as compared to the homozygous TT wild-type.Further research is needed at the functional level and in larger cohorts to determine the potential of these genes as a therapeutic target in epilepsy subjects.展开更多
BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life...BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.展开更多
文摘BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.
文摘BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of epilepsy.However,very few studies have investigated the relevance of genetic variations in epilepsy and anti-epileptic drug resistance.AIM To investigate associations between polymorphisms,rs121917953 T/A and rs121918623 C/T,and drug resistance in epilepsy patients in the north Indian population.METHODS A total of 100 age-and sex-matched epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and SCN1A rs121918623 C/T*and rs121917953 T/A*polymorphisms were analyzed by the allele specific-PCR technique.χ^(2)and Fisher’s exact test were used to estimate differences between the distribution of SCN1A rs121918623 and rs121917953 gene polymorphisms among various groups.The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.RESULTS For the SCN1A rs121917953 T/A*(D188V)polymorphism,a significantly higher proportion of individuals with AT genotype were observed in the drug-resistant group as compared to the drug-responsive group.Additionally,a higher risk association was exhibited by AT genotype for drug resistance with an odds ratio of 3.51 and P value=0.017.For the SCN1A rs121918623 C/T*(T875M)polymorphism,no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.CONCLUSION Our findings indicate that the SCN1A polymorphism D188V is associated with a higher risk of drug resistance for the AT variant as compared to the homozygous TT wild-type.Further research is needed at the functional level and in larger cohorts to determine the potential of these genes as a therapeutic target in epilepsy subjects.
文摘BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.
