Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, People’s Republic of China.
Mutagenesis. 2011 Mar;26(2):309-14. doi: 10.1093/mutage/geq095. Epub 2010 Nov 8.
In the past decade, a number of case-control studies have been carried out to investigate the relationship between the HHEX polymorphism and type 2 diabetes (T2D). However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the HHEX polymorphism and T2D. In total, 22 association studies on two HHEX polymorphisms (rs1111875 and rs7923837) and risk of T2D published before April 2010, including a total of 36 695 T2D cases and 51 800 controls were included. We also explored potential sources of heterogeneity. In a combined analysis, the summary per-allele odds ratio (OR) for T2D of the rs1111875 and rs7923837 polymorphism was 1.17 [95% confidence interval (CI): 1.13-1.21] and 1.23 (95% CI: 1.18-1.28), respectively. The haplotype analysis also showed significant association in the pooled international populations with an OR of 1.19 (95% CI: 1.15-1.22). In the subgroup analysis by ethnicity, significantly increased risks were found in Asians and Caucasians for these polymorphisms in almost all genetic models. Subgroup analysis also showed that ethnicity is the main source of heterogeneity between pooled studies. This meta-analysis demonstrated that the risk allele of HHEX polymorphisms (rs1111875 and rs7923837) is a risk factor for developing T2D. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of the HHEX gene on risk of T2D.
在过去的十年中，已经进行了许多病例对照研究来探讨 HHEX 多态性与 2 型糖尿病（T2D）之间的关系。然而，结果尚无定论。为了研究这种不一致性，我们对所有涉及 HHEX 多态性与 T2D 关系的研究进行了荟萃分析。共有 22 项关于 HHEX 两个多态性（rs1111875 和 rs7923837）与 T2D 风险的关联研究于 2010 年 4 月前发表，共纳入 36695 例 T2D 病例和 51800 例对照。我们还探讨了潜在的异质性来源。在合并分析中，rs1111875 和 rs7923837 多态性的 T2D 每等位基因优势比（OR）分别为 1.17（95%可信区间[CI]：1.13-1.21）和 1.23（95%CI：1.18-1.28）。单体型分析也显示在 pooled 国际人群中存在显著关联，OR 为 1.19（95%CI：1.15-1.22）。在按种族亚组分析中，这两种多态性在几乎所有遗传模型中均发现亚洲人和高加索人存在显著增加的风险。亚组分析还表明，种族是 pooled 研究之间异质性的主要来源。这项荟萃分析表明，HHEX 多态性（rs1111875 和 rs7923837）的风险等位基因是 T2D 发病的危险因素。然而，需要进行更大规模的研究以提供关于 HHEX 基因对 T2D 风险影响的确凿证据。
