脂联素和过氧化物酶体增殖物激活受体-γ 基因多态性及其与 2 型糖尿病的基因-基因相互作用。

Adiponectin and peroxisome proliferator-activated receptor-γ gene polymorphisms and gene-gene interactions with type 2 diabetes.

机构信息

Department of Endocrinology, The Third Hospital Affiliate to Wenzhou Medical University, Ruian, Zhejiang 325200, China; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou 325200, China.

Ruian Center of the Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou 325200, China; Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou 325035, China.

出版信息

Life Sci. 2014 Mar 7;98(1):55-9. doi: 10.1016/j.lfs.2013.12.232. Epub 2014 Jan 15.

DOI:10.1016/j.lfs.2013.12.232

PMID:24440313

Abstract

AIMS

To investigate whether gene polymorphisms of both adiponectin and peroxisome proliferator-activated receptor gamma (PPARγ) influence type 2 diabetes mellitus (T2DM) respectively in the Han people of the Wenzhou region of China and whether the interaction of gene polymorphism between adiponectin and PPARγ influences T2DM in the same subjects.

MAIN METHODS

This study included 198 patients with T2DM and 255 healthy individuals. Polymerase chain reaction-restriction fragment length polymorphism analyses were used to detect single nucleotide polymorphisms (SNPs). Logistic regression and multifactor dimensionality reduction (MDR) methods were used to analyze gene-gene interactions.

KEY FINDINGS

The frequency distribution of adiponectin SNP11377 was not different (p=0.792), but the frequency of CC, CG and GG genotypes showed the difference between two groups (T2DM: 57.1%, 33.3%, and 9.6%; control: 53.7%, 41.6%, and 4.7%, respectively; p=0.047). Adiponectin SNP45, SNP276 and PPAR γ SNPp12a were equally distributed between the two groups (p=0.586, 0.119, 0.437, respectively), and there were no significant differences in genotype frequencies between the two groups (p=0.751, 0.144, 0.479, respectively). Linkage disequilibrium existed between SNP11377 and SNP45 (p<0.001) and SNP45 and SNP276 (p<0.001). Haplotype analyses showed no significant differences between the T2DM and control groups. According to the logistic regression and MDR gene-gene interaction analyses, SNP11377GG and SNP276GT interactions increased the risk of T2DM (odds ratio=6.984, p=0.012).

SIGNIFICANCE

Adiponectin SNP11377 and SNP276 gene-gene interactions are associated with the increased risk of T2DM in this population.

摘要

目的

探讨温州汉族人群脂联素和过氧化物酶体增殖物激活受体γ（PPARγ）基因多态性是否分别影响 2 型糖尿病（T2DM），以及脂联素和 PPARγ 基因多态性之间的基因-基因相互作用是否影响同一人群的 T2DM。

方法

本研究纳入了 198 例 T2DM 患者和 255 例健康对照者。采用聚合酶链反应-限制性片段长度多态性分析方法检测单核苷酸多态性（SNP）。采用 logistic 回归和多因子降维（MDR）方法分析基因-基因相互作用。

主要发现

脂联素 SNP11377 的频率分布在两组间无差异（p=0.792），但 CC、CG 和 GG 基因型的频率存在差异（T2DM：57.1%、33.3%和 9.6%；对照组：53.7%、41.6%和 4.7%；p=0.047）。脂联素 SNP45、SNP276 和 PPARγSNPp12a 在两组间的分布均等（p=0.586、0.119、0.437），两组间基因型频率无显著差异（p=0.751、0.144、0.479）。SNP11377 与 SNP45（p<0.001）和 SNP45 与 SNP276（p<0.001）之间存在连锁不平衡。单体型分析显示，T2DM 组与对照组之间无显著差异。根据 logistic 回归和 MDR 基因-基因相互作用分析，SNP11377GG 和 SNP276GT 相互作用增加了 T2DM 的风险（比值比=6.984，p=0.012）。