TM6SF2、PCSK9 和 PCSK7 基因变异与肝移植后肝脂肪变性的风险：一项横断面研究。

Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study.

机构信息

Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Transplant Research Center, Shiraz University of Medical Sciences, Research Tower, PO Box 71994-67985, Shiraz, Iran.

出版信息

BMC Gastroenterol. 2021 Dec 7;21(1):458. doi: 10.1186/s12876-021-02041-8.

DOI:10.1186/s12876-021-02041-8

PMID:34876018

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8650293/

Abstract

BACKGROUND

Genetic abnormalities might have important role in pathogenesis of hepatic steatosis after liver transplantation. We aimed to investigate association between genetic variations in transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, proprotein convertase subtilisin/kexin type 9 (PCSK9) rs505151 and proprotein convertase subtilisin/kexin type 7 (PCSK7) rs2277287 with hepatic steatosis in liver transplant recipients.

METHODS

In a cross-sectional study, adult (> 18 years) liver transplant recipients who were referred for their routine post-transplant follow-up between June 2018 and September 2018 were included in the study. Hepatic steatosis in transplant recipients was assessed by controlled attenuation parameter (CAP). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to study TM6SF2 rs58542926, PCSK7 rs2277287 and PCSK9 rs505151 genotypes.

RESULTS

107 liver transplant recipients were included. There was no association between different genotypes of PCSK9 rs505151 and PCSK7 rs2277287 with hepatic steatosis in liver transplant recipients (P value > 0.05). The presence of TT genotype of TM6SF2 rs58542926 was higher in patients with hepatic steatosis measured by CAP after liver transplantation. In patients with moderate and severe hepatic steatosis (grade 2 and 3 steatosis), AG + GG genotypes of PCSK9 rs505151 were more prevalent than AA genotype (OR 8.667; 95% CI 1.841-40.879; P value = 0.004) compared to patients with mild steatosis (grade 1). In multivariate regression model, AG + GG genotypes of PCSK9 rs505151 were associated with moderate and severe steatosis in liver transplant recipients (OR 5.747; 95% CI 1.086-30.303; P value = 0.040).

CONCLUSIONS

Genetic variations in TM6SF2 rs58542926 and PCSK9 rs505151 might be associated with hepatic steatosis in liver transplant recipients.

摘要

背景

遗传异常可能在肝移植后肝脂肪变性的发病机制中起重要作用。我们旨在研究跨膜 6 超家族成员 2（TM6SF2）rs58542926、前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）rs505151 和前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 7（PCSK7）rs2277287 基因变异与肝移植受者肝脂肪变性之间的关系。

方法

在一项横断面研究中，纳入了 2018 年 6 月至 2018 年 9 月期间因常规移植后随访而就诊的成年（>18 岁）肝移植受者。通过受控衰减参数（CAP）评估移植受者的肝脂肪变性。聚合酶链反应-限制性片段长度多态性（PCR-RFLP）用于研究 TM6SF2 rs58542926、PCSK7 rs2277287 和 PCSK9 rs505151 基因型。

结果

共纳入 107 例肝移植受者。PCSK9 rs505151 和 PCSK7 rs2277287 的不同基因型与肝移植受者的肝脂肪变性之间无相关性（P 值>0.05）。TM6SF2 rs58542926 的 TT 基因型在肝移植后通过 CAP 测量的肝脂肪变性患者中更为常见。在中重度肝脂肪变性（2 级和 3 级脂肪变性）患者中，与轻度脂肪变性（1 级）患者相比，PCSK9 rs505151 的 AG+GG 基因型更为常见（OR 8.667；95%CI 1.841-40.879；P 值=0.004）。在多变量回归模型中，PCSK9 rs505151 的 AG+GG 基因型与肝移植受者的中重度脂肪变性相关（OR 5.747；95%CI 1.086-30.303；P 值=0.040）。