AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no...AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no diabetes or additional disease(Group C), 20 cataract patients with diabetes and no retinopathy(Group DM+C), and 20 cataract patients with diabetic retinopathy(Group DR+C).All the patients were examined with respect to body mass index(BMI), fasting plasma glucose, hemoglobin A1c(HbA1c), and lipid profile.Phacoemulsification and intraocular lens(Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation.The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays.RESULTS: A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels(P<0.05 for all parameters tested).The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C(P<0.001, P=0.004).No statistically significant difference was determined in the aqueous adiponutrin levels in three groups.The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C(both P=0.001).The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C(P=0.001, P<0.001).CONCLUSION: Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance.The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.展开更多
Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tentl...Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.展开更多
AIMTo investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODSCaucasian heavy drinkers (n = 521) wi...AIMTo investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODSCaucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease (steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 patients. RESULTSThe PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis (r = 0.404, P r = 0.319, P r = 0.264, P r = 0.828, P r = 0.516, P r = 0.319, P vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to develop cirrhosis corrected for age, gender and body mass index was 1.295 (95%CI: 0.787-2.131) for CG + GG carriers. CONCLUSIONIn heavy drinkers, PNPLA3 GG primarily correlates with ballooning/steatohepatitis but not steatosis resulting in a delayed inflammation-associated resolution of LS. Consequently, sustained ballooning-associated LS elevation seems to be a potential risk factor for fibrosis progression in PNPLA3 GG carriers.展开更多
文摘AIM: To evaluate plasma and aqueous levels of adiponutrin and pannexin 1 in patients with and without diabetic retinopathy.METHODS: The study included three age and gendermatched groups of 20 cataract patients with no diabetes or additional disease(Group C), 20 cataract patients with diabetes and no retinopathy(Group DM+C), and 20 cataract patients with diabetic retinopathy(Group DR+C).All the patients were examined with respect to body mass index(BMI), fasting plasma glucose, hemoglobin A1c(HbA1c), and lipid profile.Phacoemulsification and intraocular lens(Phaco+IOL) implantation were performed to all patients in all the groups, and aqueous samples were taken during the operation.The plasma and aqueous adiponutrin and pannexin 1 levels were analyzed using enzyme-linked immunosorbent assays.RESULTS: A statistically significant difference was determined between the groups with respect to BMI, fasting plasma glucose, and HbA1c levels(P<0.05 for all parameters tested).The plasma adiponutrin levels of Group DR+C were statistically significantly lower than those of Group C and Group DM+C(P<0.001, P=0.004).No statistically significant difference was determined in the aqueous adiponutrin levels in three groups.The plasma pannexin 1 levels of Groups DM+C and DR+C were statistically significantly lower than those of Group C(both P=0.001).The aqueous pannexin 1 levels of Group DR+C were statistically significantly higher than those of Group C and Group DM+C(P=0.001, P<0.001).CONCLUSION: Adiponutrin and pannexin 1, which play an important role in the pathophysiology of diabetes and obesity, and have a regulatory role in hyperglycemia and insulin resistance.The measurement of adiponutrin and pannexin 1 levels may support clinicians in determining the risk of DR development.
基金Supported by Grants PICT 2008-1521 and PICT 2010 0441,from National Agency for Science and TechnologyUBACYT CM04,from Universidad de Buenos AiresSookoian S and Pirola CJ belong to National Council of Scientific and Technical Research
文摘Genome-wide and candidate gene association studies have identified several variants that predispose indi- viduals to developing nonalcoholic fatty liver disease （NAFLD）. However, the gene that has been consis- tently involved in the genetic susceptibility of NAFLD in humans is patatin-like phospholipase domain contain- ing 3 （PNPLA3, also known as adiponutrin）. A nonsyn- onymous single nucleotide polymorphism in PNPLA3 （rs738409 C/G, a coding variant that encodes an amino acid substitution I148M） is significantly associated with fatty liver and histological disease severity, not only in adults but also in children. Nevertheless, how PNPLA3 influences the biology of fatty liver disease is still an open question. A recent article describes new aspects about PNPLA3 gene/protein function and suggests that the I148M variant promotes hepatic lipid synthesis due to a gain of function. We revise here the published data about the role of the I148M variant in lipogen- esis/lipolysis, and suggest putative areas of future research. For instance we explored in silico whether the rs738409 C or G alleles have the ability to modify miRNA binding sites and miRNA gene regulation, and we found that prediction of PNPLA3 target miRNAs shows two miRNAs potentially interacting in the 3＇ UTR region （hsa-miR-769-3p and hsa-miR-516a-3p）. In addition, interesting unanswered questions remain to be explored. For example, PNPLA3 lies between two CCCTC-binding factor-bound sites that could be tested for insulator activity, and an intronic histone 3 lysine 4 trimethylation peak predicts an enhancer element, cor- roborated by the DNase I hypersensitivity site peak. Finally, an interaction between PNPLA3 and glycerol- 3-phosphate acyltransferase 2 is suggested by data miming.
基金The German Research Foundation(DFG,RA-2677/1-1)the Dietmar Hopp-Foundation,no.2301196
文摘AIMTo investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness (LS) during alcohol withdrawal and its association with histology. METHODSCaucasian heavy drinkers (n = 521) with a mean alcohol consumption of 192.1 g/d (median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem Medical Center, University of Heidelberg. LS was measured by transient elastography (Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease (steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 patients. RESULTSThe PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis (r = 0.404, P r = 0.319, P r = 0.264, P r = 0.828, P r = 0.516, P r = 0.319, P vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to develop cirrhosis corrected for age, gender and body mass index was 1.295 (95%CI: 0.787-2.131) for CG + GG carriers. CONCLUSIONIn heavy drinkers, PNPLA3 GG primarily correlates with ballooning/steatohepatitis but not steatosis resulting in a delayed inflammation-associated resolution of LS. Consequently, sustained ballooning-associated LS elevation seems to be a potential risk factor for fibrosis progression in PNPLA3 GG carriers.
