TM6SF2 rs58542926 E167K单核苷酸多态性与非酒精性脂肪性肝病易感性的关系

The relationship between TM6SF2 rs58542926 E167K single nucleotide polymorphisms and the susceptibility of non-alcoholic fatty liver disease

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种常见疾病,目前除了肥胖、高脂血症、糖尿病及胰岛素抵抗等危险因素外,遗传因素在其发病中起到的作用越来越受到重视。近期发现的TM6SF2 rs58542926 E167K单核苷酸多态性(single nucleotide polymorphisms,SNPs)与NAFLD的易感性明显相关,且有研究显示其与非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)、肝纤维化及肝细胞癌(hepatocellular carcinoma,HCC)的发生同样相关。目前认为TM6SF2在体内参与肝细胞脂肪代谢,与极低密度脂蛋白(very low-density lipoprotein,VLDL)的分泌有关,TM6SF2 rs58542926 E167K突变导致该蛋白功能丧失,引起肝脏甘油三酯(triglyceride,TG)的过度积累,导致NAFLD的发生。

Non-alcoholic fatty liver disease（NAFLD） is a common disease,which is absolutely associated with features of the metabolic syndrome,including obesity,dyslipidaemia,type 2 diabetes mellitus（ T2DM） and glucose intolerance. Much ongoing research is focused on identifying the genetic factors which contribute to NAFLD pathogenesis.Recently,TM6SF2 rs58542926 E167 K single nucleotide polymorphisms（ SNPs） are demonstrated to be associated with NAFLD,the morbidity of nonalcoholic steatohepatitis（ NASH）,cirrhosis and hepatocellular carcinoma（ HCC）.TM6SF2 is required for very low-density lipoprotein（ VLDL） secretion and TM6SF2 rs58542926 E167 K variant leads to lose the function of TM6SF2,which causally contributes to the attack of NAFLD.