中国汉族人群PNPLA3 I148M多态性影响脂联素水平及非酒精性脂肪性肝病遗传易感性的相关性研究(英文)  

Research Based on Effects of PNPLA3 I148M Polymorphisms on Adiponectin Levels and Genetic Susceptibility of Nonalcoholic Fatty Liver Disease in Chinese Han Population

作　　者：徐静[1] 辛永宁[1] 张丁丁[1] 宣世英[1] 

机构地区：[1]青岛大学医学院,山东青岛266021

出　　处：《现代生物医学进展》2012年第13期2451-2456,共6页Progress in Modern Biomedicine

基　　金：Natural Science Foundation of China(81170337/H0304)~~

摘　　要：目的：探讨在中国人群中PNPLA3 I148M基因型、脂联素与非酒精性脂肪性肝病的遗传易感性的相关性,及PNPLA3基因型与空腹血清脂联素水平的关系。方法：对96例NAFLD患者和76名正常对照,采用多聚酶链反应（PCR）及直接测序法检测PNPLA3基因型。计量资料结果均用均数±标准差（X±S）表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行X2检验。结果：中国汉族人群中,存在PNPLA3基因I148M多态性,I148M G等位基因频率分布在NAFLD（64.89%）与正常对照组（34.87%）、NASH组（71.70%）与SS组（56.09%）中比较差异均有统计学意义（P〈0.05）。病例对照分析显示：148GG基因携带者与148CC基因携带者相比较,前者发生NAFLD的比值比（OR）为3.45（95%CI：2.21~5.41,P〈0.05）,发生NASH的OR为1.98（95%CI=1.08~3.64,P〈0.05）。PNPLA3基因rs738409多态性与血清ALT水平有关（P〈0.05）,对NASH组分层分析,148GG基因型BMI、ALT、FINS均高于148CC基因型（P〈0.05）,血清HDL水平低于148CC基因型和148GC基因型（P〈0.05）,这些结果提示等位基因G与肝脏炎症和肝脏脂肪增加有相关性.Ordinal Logistic回归分析显示PNPLA3 I148M多态性与低浓度血清脂联素水平相关（〈6μg/ml）（OR=2.78,95%CI=1.765~4.384,P〈0.05）。结论：中国汉族人群中,PNPLA3基因I148M多态性与NAFLD的遗传易感性及脂联素的分泌调节相关,是决定NAFLD个体遗传易感性的重要因素。Objective： To investigate the relationship between PNPLA3 I148M genotype,adiponectin and hereditariness to nonal-coholic fatty liver disease,and to evaluate the effect of PNPLA3 genotype on fasting levels of adiponectin in China.Methods： Genotypes of 94 case patients with NAFLD and 76 control subjects were examined by polymerase chain reaction（PCR） and directly sequenced.The DNA samples were extracted from the peripheral blood of all subjects.Adiponectin by ELISA.All measurement data results were shown by the mean ±the standard deviation（X±S）.A T-test was carried out following the homogeneity test of variance.The comparison of gender,genotype and allele frequency was analyzed by the Chi-square test.Results： The SNP,I148M were indentified with frequen-cies of variant alleles 64.89%,71.70% and 56.09% in patients with NAFLD,NASH and SS and 34.87% in control,respectively.A case-control analysis revealed a 3.45-fold（95%CI：2.21~5.41） excessed risk of developing NAFLD for 148GG genotype carriers com-pared with noncarriers.And 1.98-fold（95%CI=1.08~3.64） excessed risk of SS developing NASH for 148GG genotype compared with noncarriers.Polymorphism in PNPLA3 rs738409 was associated with the levels of ALT in serum（P〈0.05）.BMI,ALT,FINS in patients with148GG genotype were higher than 148CC genotype（P〈0.05）,but the serum levels of HDL were lower than 148CC genotype and 148GC genotype（P〈0.05）.At ordinal logistic regression analysis,the PNPLA3 148M variant was associated with low adiponectin levels（〈 6 μg/ml）（OR=2.78,95%CI=1.765~4.384,P〈0.05）.Conclusion： The results suggested that the I148M genetic variants in PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD and the release of adiponectin in Chinese population.Polymorphism in PNPLA3 gene I148M are related with development of NAFLD,are the significance factors of the susceptibility of NAFLD.

关 键 词：非酒精性脂肪性肝病 脂联素 PNPLA3 单核苷酸多态性 

分 类 号：Q347[生物学—遗传学]