非酒精性脂肪性肝病相关基因的单核苷酸多态性研究

The Study on Single Nucleotide Polymorphisms of Non-alcoholic Fatty Liver Disease Correlated Gene

背景与目的:探讨载脂蛋白B(ApolpoproteinB,ApoB)、β3-肾上腺素能受体(β3-adrenergicreceptor,β3-AR)、细胞色素P4502E1(cytochromeP4502E1,CYP2E1)基因单核苷酸多态性与非酒精性脂肪性肝病(Non-alcoholicfattyliverdisease,NAFLD)发病的关系,并从分子水平探讨该病的发病机制。材料与方法:应用聚合酶链反应和基因芯片技术,对194例NAFLD患者和189例健康对照的ApoB、β3-AR、CYP2E1基因多态性进行了分析。结果:轻度NAFLD组ApoBMspⅠ位点M+M-基因型频率(18.6%)和等位基因型频率(9.3%)均高于对照组(分别为10.3%和5.2%),差别有统计学意义(P<0.05)。ApoBMspⅠ和CYP2E1基因多态性的联合作用使中重度脂肪肝发病的危险性增加近4倍。结论:ApoBMspⅠ位点多态性与轻度NAFLD有关,CYP2E1和ApoBMspⅠ基因多态性的联合作用分析从分子水平解释了NAFLD发生发展的机制,同时也为研究NAFLD遗传易感性从方法学上提供了新的思路。

BACKGROUND ＆ AIM： To study the Apolipoprotein B gene（ApoB）,β3-adrenergic receptor gene （β3-AR）,cytochrome P4502E1（CYP2E1） gene polymorphisms and their relationship with non-alcoholic fatty liver disease（NAFLD）.MATERIAL AND METHODS： The single nucleotide polymorphisms（SNPs） of Apo BMsp Ⅰsite, β3-AR Trp64Arg site and CYP2E1 PstI and RsaI sites were studied using the technique of polymerase chain reaction and gene chips in a sample of 189 healthy individuals and 194 patients with NAFLD. RESULTS： The frequency of the mutant genotype M^＋M^- and the rarer allele M^- of the Apo BMsp Ⅰ site was significantly higher among mild NAFLD patients （18.6% and 9.3% respectively） than among controls（10.3% and 5.2% respectively）. The combined effect of ApoB with CYP2E1 increase the risk of severe NAFLD almost 4 fold. CONCLUSION： ApoB Msp Ⅰ gene polymorphisms was likely to be associated with the occurrence of mild NAFLD. The analysis of combined effect of gene polymophisms did not only explain the pathogenesis of NAFLD at a molecular level, but also provided a new method for related future research.