TM6SF2 E167K 和 PNPLA3 I148M 变异体在东北地区非酒精性脂肪性肝病中的相互作用。

Interaction of TM6SF2 E167K and PNPLA3 I148M variants in NAFLD in northeast China.

机构信息

Department of Medicine, Division of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Ann Hepatol. 2019 May-Jun;18(3):456-460. doi: 10.1016/j.aohep.2018.10.005. Epub 2019 Apr 15.

DOI:10.1016/j.aohep.2018.10.005

PMID:31054977

Abstract

INTRODUCTION AND AIM

This study aimed to confirm the association of the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant with non-alcoholic fatty liver disease (NAFLD) and the degree of steatosis, as well as the additive effect of body mass index (BMI) or the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M and TM6SF2 E167K variants in NAFLD.

MATERIALS AND METHODS

A total of 158 NAFLD patients and 158 matched controls were recruited. Steatosis was classified as mild, moderate and severe by FibroScan. Associations between the TM6SF2 E167K variant and NAFLD as well as clinical parameters were evaluated.

RESULTS

Although the frequency of the T allele was low in the Chinese population (MAF=7.4%), there was still a significant association between the E167K variant and NAFLD (odds ratio=3.379, 95% confidence interval: 1.500-7.612, P=0.003). In particular, the TM6SF2 genotype was also associated with the degree of steatosis (P=0.023). The TM6SF2 variant was associated with increased alanine aminotransferase (ALT) but no other clinical parameters, such as aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lipids. Notably, we also found that an additive effect of the TM6SF2 E167K and PNPLA3 I148M variants in NAFLD. Furthermore, we did not identify an association between the TM6SF2 E167K variant and NAFLD in the non-obese population.

CONCLUSION

The TM6SF2 E167K variant was associated with NAFLD in northeast China, and there was an interaction between the PNPLA3 I148M and TMS6F2 E167K variants in NAFLD.

摘要

介绍和目的

本研究旨在证实跨膜 6 超家族成员 2（TM6SF2）E167K 变体与非酒精性脂肪性肝病（NAFLD）和脂肪变性程度的关联，以及体重指数（BMI）或 patatin-样磷脂酶域包含蛋白 3（PNPLA3）I148M 和 TM6SF2 E167K 变体在 NAFLD 中的附加效应。

材料和方法

共招募了 158 例 NAFLD 患者和 158 例匹配对照。通过 FibroScan 将脂肪变性分为轻度、中度和重度。评估 TM6SF2 E167K 变体与 NAFLD 以及临床参数之间的关联。

结果

尽管 TM6SF2 E167K 变体在中国人群中的等位基因频率较低（MAF=7.4%），但它仍然与 NAFLD 显著相关（比值比=3.379，95%置信区间：1.500-7.612，P=0.003）。特别是，TM6SF2 基因型也与脂肪变性程度相关（P=0.023）。TM6SF2 变体与丙氨酸氨基转移酶（ALT）升高相关，但与天门冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）和脂质等其他临床参数无关。值得注意的是，我们还发现 TM6SF2 E167K 和 PNPLA3 I148M 变体在 NAFLD 中的附加效应。此外，我们没有发现 TM6SF2 E167K 变体与非肥胖人群中 NAFLD 之间的关联。