脂联素基因多态性与非酒精性脂肪肝及其代谢紊乱的关系

Association between adiponectin gene polymorphisms and Non-alcoholic fatty liver

目的探讨脂联素单核苷酸多态性SNP45T→G和SNP276G→T与非酒精性脂肪肝及其合并代谢紊乱的相关性。方法以PCR-RFLP技术,对408例研究对象脂联素基因SNP45、SNP276多态性进行基因分型,其中264例(亚组)测定BMI、FBS、ALT、TC、TG和FINS、脂联素水平,计算HOMA-IR。结果(1)SNP45和SNP276两个多态性位点的基因型和等位基因频率在非酒精性脂肪肝组、非酒精性脂肪肝合并代谢紊乱组和对照组中的分布无显著差异;(2)在亚组受试人群中,SNP45位点为GG或GT者的TG、FBS高于T/T者;在对照组中,SNP45位点为GG或GT者的TG高于T/T者;在非肥胖组SNP45位点为GG或GT者的HOMA指数、BMI、TG及ALT高于T/T者(P<0.05);(3)在非肥胖组SNP276位为GG或GT者的HOMA高于T/T者(P<0.005),G/G者的BMI大于GT或TT者(P<0.05);(4)在亚组、非肥胖组和正常组SNP45位点为GG或GT者的脂联素水平较T/T者低,没有发现SNP276G/T基因型与脂联素水平之间的差异。结论脂联素基因SNP45和276多态性与武汉地区汉族人群中非酒精性脂肪肝无明显相关性。在非肥胖组脂联素基因SNP45、SNP276变异与IR、BMI相关,脂联素基因SNP45变异对脂联素水平、TG、FBS和ALT的代谢产生影响。

Objective The aim of the study is to investigate the effect of SNP45 and SNP276 of the adiponectin gene on non-alcoholic fatty liver disease（ NAFLD）, NAFLD with metabolic disorders（MD） and to assess whether adiponectin gene variants contribute to clinical variables, insulin resistance （IR）or circulating adiponectin. Methods 165 non-alcoholic fatty liver subjects, 83 NAFLD patients with meta- bolic disorders, and 160 healthy controls were genotyped for SNPs 45T 〉 G and 276G 〉 T. A subgroup of 117 patients with NAFLD ,71 NAFLD patients with metabolic disorders ,76 healthy controls were measured anthropometric and biochemical variables by routine methods and determined serum adiponectin and insulin levels. Insulin resistance indexes were assessed by the HOMA-IR. Results （ 1 ） No association of single nucleotide polymorphism 45 or 276 was found in NAFLD or NAFLD with metabolic disorders. （2） At the SNP 45, subjects with GG or GT genotype in all subgroup had significantly higher concentrations of TG,FBS than did T/T subjects;Subjects with the GG or GT genotype in health controls had significantly higher TG than did T/T subjects ;In subjects with BMI 〈 25 kg/m^2, subjects with the GG or GT genotype had significantly higher HOMA,BMI,TG and ALT than did T/T subjects. Subjects with GG or GT genotype had lower adiponectin concentrations than did T/T subjects in subgroup subjects, health controls and normal BMI subjects. （3）At the SNP 276, subjects with GG or GT genotype had significantly higher HOMA than did T/T subjects, subjects with the GG genotype had significantly higher BMI than did GT or TT subjects, no association was found between adiponectin G276T gene variants and circulating adiponectin concentrations. Conclusions The T45G and G276T of the adiponectin gene may not be an important determinant of NAFLD in Chinese people, but they influence plasma lipid levels, FBS, insulin resistance, BMI,ALT and serum adiponectin concentrations.