高砷环境下非酒精性脂肪性肝病人群的遗传易感性与尿砷代谢特点

Genetic Susceptibility to Non-alcoholic Fatty Liver Disease and Characteristics of Urinary Arsenic Metabolism in a High Arsenic Environment

目的探讨在高砷环境下非酒精性脂肪性肝病(NAFLD)人群的遗传易感性与尿砷代谢特点。方法2010年对山西省和内蒙古自治区饮水型砷中毒病区居民开展流行病学调查和血液、尿液等生物样本采集,以影像诊断结果及饮酒习惯判断受试者是否患有NAFLD,采用单核苷酸多态性(SNP)scan TM多重SNP分型试剂盒对SNP进行基因分型,采用氢化物发生原子荧光法测定尿砷含量,使用Logistic回归模型分析脂代谢基因多态性与疾病易感性的关联。结果排除未获得SNP检测结果和不满足本研究纳入标准者,共有120名研究对象纳入本研究,其中30例NAFLD患者作为病例组,90名健康者作为对照组。两组载脂蛋白(Apo)B、瘦素受体、含Patatin样磷脂酶域蛋白3(PNPLA3)、脂联素、脂肪酸结合蛋白、肝脂酶、ApoA、低密度脂蛋白受体等位基因分布频率比较差异无统计学意义(P>0.05)。PNPLA3/rs12483959多态性与砷暴露地区NAFLD患病存在关联,携带GA基因型的个体患NAFLD的风险是携带野生纯合型GG个体的2.359倍(P<0.05),携带GA+AA基因型的个体患NAFLD的风险是携带野生纯合型GG个体的2.663倍(P<0.05),其余位点均与NAFLD患病无明显关联(P>0.05)。病例组的一甲基化率显著低于对照组[2.6(1.4,3.2)比3.7(1.0,5.2)](P<0.05),一甲基化指数高于对照组(0.89±0.12比0.85±0.13)(P<0.05)。结论高砷环境下PNPLA3基因rs12483959位点GA、GA+AA基因型可能增加NAFLD的患病风险,NAFLD人群与非NAFLD人群的尿砷代谢模式存在较大差异。

Objective To discuss the genetic susceptibility to non-alcoholic fatty liver disease(NAFLD)and characteristics of urinary arsenic metabolism in a high arsenic environment.Methods In 2010,an epidemiological survey and the collection of blood,urine and other biological samples were carried out among residents in drinking water arsenism areas in Shanxi Province and Inner Mongolia Autonomous Region.Imaging diagnosis results and drinking habits were used for NAFLD diagnosis;single nucleotide polymorphism(SNP)scan TM multiple SNP parting kit was adopted for SNP genotyping;urinary arsenic content was determined by hydride generation atomic fluorescence method;Logistic regression model was used to analyze the association between lipid metabolism gene polymorphism and the susceptibility.Results Excluding those who did not obtain SNP test results and were not satisfied with the inclusion criteria of this study,a total of 120 subjects were included in this study,including 30 NAFLD patients as the case group and 90 healthy subjects as the control group.There was no significant difference in the allele frequencies of apolipoprotein(Apo)B,leptin receptor,Patatin-like phospholipase domain containing 3(PNPLA3),ADIPOQ,fatty acid-binding protein,LIPC,ApoA and low-density lipoprotein receptor between the two groups(P>0.05).PNPLA3/rs12483959 polymorphism was associated with NAFLD in arsenic exposed areas.Individuals carrying the GA genotype had a 2.359-fold higher risk of developing NAFLD than individuals carrying wild homozygous GG(P<0.05).Individuals carrying the GA+AA genotype had a 2.663-fold risk of developing NAFLD than individuals carrying wild homozygous GG(P<0.05).The other loci were not significantly associated with NAFLD(P>0.05).The primary methylation rate of the case group was significantly lower than that of the control group[2.6(1.4,3.2)vs 3.7(1.0,5.2)](P<0.05),and the primary methylation index of the case group was significantly higher than that of the control group(0.89±0.12 vs 0.85±0.13)(P<0.05).Conclusion GA,GA+AA genotypes of PNPLA3/rs12483959 may increase the risk of NAFLD in high arsenic environment.Urinary arsenic metabolism patterns in the NAFLD population and non-NAFLD population are significantly different.