中国南方地区 2 型糖尿病与 DRD3、COMT 和 SLC6A4 基因多态性的关联：一项基于医院的病例对照研究。

Association of DRD3, COMT, and SLC6A4 Gene Polymorphisms with Type 2 Diabetes in Southern Chinese: A Hospital-Based Case-Control Study.

机构信息

1 Department of Epidemiology and Medical Statistics, School of Public Health, and Institute of Medical Systems Biology, Guangdong Medical College , Dongguan, Guangdong, China .

2 Department of Endocrinology and Metabolism, Maoming People's Hospital , Maoming, Guangdong, China .

出版信息

Diabetes Technol Ther. 2015 Aug;17(8):580-6. doi: 10.1089/dia.2014.0344. Epub 2015 Apr 30.

DOI:10.1089/dia.2014.0344

PMID:25927430

Abstract

AIM

The aim of this study was to assess the associations of six single nucleotide polymorphisms (SNPs) of three genes (DRD3, COMT, and SCL6A4) with type 2 diabetes mellitus (T2DM) in Southern Chinese.

SUBJECTS AND METHODS

Five hundred ninety-five cases with T2DM and 725 healthy controls of Han origin were recruited from six hospitals in Guangdong Province, Southern China. Fasting serum concentrations of markers of interest (total cholesterol, triglyceride, plasma glucose, etc.) were measured in hospitals. SNP genotyping was performed using a custom-by-design 2-×48-Plex SNPscan™ kit (Genesky Biotechnologies Inc., Shanghai, China). Single-point SNP analysis, haplotype analysis, and SNP-SNP interactions were carried out.

RESULTS

SNP rs4646312 in COMT achieved statistical significance in both allelic association and genotypic association and even after adjusting covariates (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.04-1.53; P=0.021). Two haplotypes consisting of rs4646312 and rs4680 were also significantly associated with T2DM, of which C-G was a protective haplotype for T2DM (OR=0.83; 95% CI, 0.70-0.98; P=0.029), whereas T-A was a risk one (OR=1.23, 95% CI, 1.03-1.46; P=0.022). Interaction analysis identified a significant epistatic effect between rs4680 in COMT and rs2066713 in SCL6A4 after adjusting for covariates (OR=3.59, 95% CI, 1.72-7.48; P=0.001 for dominant-dominant model). However, only the interaction between rs4680 and rs2066713 was significant, and haplotype T-A showed a marginally increased risk after Bonferroni correction.

CONCLUSIONS

The genetic polymorphisms in COMT and SCL6A4 confer significant effects in joint actions to T2DM in Southern Chinese.

摘要

目的

本研究旨在评估三个基因（DRD3、COMT 和 SCL6A4）的 6 个单核苷酸多态性（SNP）与中国南方 2 型糖尿病（T2DM）的关联。

受试者和方法

从中国南方广东省的六家医院招募了 595 例 T2DM 患者和 725 名健康对照者（汉族）。在医院测量了感兴趣的标志物（总胆固醇、甘油三酯、血浆葡萄糖等）的空腹血清浓度。使用定制的 2×48-Plex SNPscan™试剂盒（Genesky Biotechnologies Inc.，上海，中国）进行 SNP 基因分型。进行单点 SNP 分析、单倍型分析和 SNP-SNP 相互作用分析。

结果

COMT 中的 SNP rs4646312 在等位基因关联和基因型关联方面均具有统计学意义，即使在调整了协变量后（比值比[OR]=1.26；95%置信区间[CI]，1.04-1.53；P=0.021）。由 rs4646312 和 rs4680 组成的两个单倍型也与 T2DM 显著相关，其中 C-G 是 T2DM 的保护单倍型（OR=0.83；95%CI，0.70-0.98；P=0.029），而 T-A 是风险单倍型（OR=1.23，95%CI，1.03-1.46；P=0.022）。在调整协变量后，交互分析确定 COMT 中的 rs4680 和 SCL6A4 中的 rs2066713 之间存在显著的上位性效应（OR=3.59，95%CI，1.72-7.48；P=0.001 用于显性-显性模型）。然而，只有 rs4680 与 rs2066713 之间的相互作用具有统计学意义，并且在 Bonferroni 校正后，单倍型 T-A 显示出略微增加的风险。