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MTTP 多态性与汉族人群非酒精性脂肪性肝病易感性的关系。

MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population.

机构信息

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.

出版信息

Liver Int. 2014 Jan;34(1):118-28. doi: 10.1111/liv.12220. Epub 2013 Jun 5.

Abstract

BACKGROUND

The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein B (ApoB)-containing lipoproteins from the liver and intestine. Previous studies showed that functional polymorphisms in the MTTP gene correspond to lower LDL levels and protect against other traits of the metabolic syndrome.

AIMS

Here, we aimed to investigate whether MTTP single nucleotide polymorphisms (SNPs) and their predicted haplotypes of linkage disequilibrium blocks contribute to non-alcoholic fatty liver disease (NAFLD) susceptibility in a Han Chinese population.

METHODS

Seven tag SNPs in the MTTP gene were selected and genotyped in a frequency-matched case-control study in a population from Fuzhou City, China. We enrolled 580 patients with NAFLD and 580 healthy controls.

RESULTS

In the multivariate logistic regression analysis, the rs1800804 (-164 T/C) was associated with an increased risk of NAFLD, while the rs1057613 A/G and rs3805335 C/T SNPs were associated with a decreased risk of NAFLD. The cumulative effect of the rs1800804 (-164 T/C), rs1057613 and rs3805335 was estimated, and a significant increased trend in the risk of NAFLD with increasing genetic risk score was observed (adjusted P(trend) = 0.014). Furthermore, the results of haplotype analysis suggested that the haplotype GC in block 1 containing the -164 C allele was associated with an increased risk of NAFLD, while haplotype TGTTC in block 2 was associated with a decreased risk of NAFLD.

CONCLUSIONS

Our data show that MTTP genetic polymorphisms influence the susceptibility to developing NAFLD independently or jointly in the Han Chinese population.

摘要

背景

微粒体甘油三酯转移蛋白(MTP)是肝脏和肠道中载脂蛋白 B(ApoB)含脂蛋白组装和分泌所必需的。先前的研究表明,MTTP 基因中的功能多态性与 LDL 水平降低相关,并可预防代谢综合征的其他特征。

目的

本研究旨在探讨 MTTP 单核苷酸多态性(SNP)及其预测的连锁不平衡块单倍型是否与汉族人群中非酒精性脂肪性肝病(NAFLD)易感性相关。

方法

在中国福州市人群中进行了一项频数匹配的病例对照研究,选择 MTTP 基因中的 7 个标签 SNP 进行基因分型。共纳入 580 例 NAFLD 患者和 580 例健康对照。

结果

多变量 logistic 回归分析显示,rs1800804(-164 T/C)与 NAFLD 风险增加相关,而 rs1057613 A/G 和 rs3805335 C/T SNP 与 NAFLD 风险降低相关。rs1800804(-164 T/C)、rs1057613 和 rs3805335 的累积效应进行了估计,随着遗传风险评分的增加,NAFLD 的风险呈显著增加趋势(调整后 P(趋势)=0.014)。此外,单倍型分析结果表明,第 1 块中包含-164 C 等位基因的 GC 单倍型与 NAFLD 风险增加相关,而第 2 块中的 TGTTC 单倍型与 NAFLD 风险降低相关。

结论

本研究数据表明,MTTP 遗传多态性独立或共同影响汉族人群发生 NAFLD 的易感性。

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