Laboratory of Disorder Genes and Department of Pharmacology, College of Pharmacy, Chongqing Medical University, P.O. 380, 1 Yi Xue Yuan Road, Chongqing 400016, People's Republic of China.
Mol Biol Rep. 2012 Feb;39(2):1609-16. doi: 10.1007/s11033-011-0900-5. Epub 2011 May 31.
Cyclin-dependent kinase inhibitor-2A/B (CDKN2A/B) has been reported as a candidate gene of type 2 diabetes (T2D) based on its chromosomal position and its important role in β-cell function and regeneration. However, studies to date have reported inconsistent findings regarding the association between T2D and CDKN2A/B. To clarify this inconsistence, we conducted a meta-analysis based on alleles and genotypes prevalence of rs10811661 and rs564398 in CDKN2A/B. The PubMed, EMBASE, and Medline databases were systematically reviewed for studies published between January, 2006, and November, 2010. A total of 35 reports were collected, among of them only 16 studies (including 24,407 cases and 33,937 controls) match the inclusion criteria and were selected for the statistical test. In the meta-analysis of published data, our results suggest that the rs10811661 T allele (OR 1.28, 95% CI 1.21-1.36, P < 1 × 10(-5)) and TT genotype (OR 1.32, 95% CI 1.22-1.43, P < 1 × 10(-5)) of CDKN2A/B were associated with type 2 diabetes respectively, but rs564398 was not (for allele only: OR 0.96, 95% CI 0.88-1.05, P = 0.35). The association between rs10811661 T allele and T2D was observed both in Asia (P < 1 × 10(-4)) and Europe ethnicity groups (P = 0.002). This meta-analysis yielded evidence that rs10811661 of CDKN2A/B confers risk for T2D. Larger studies with mixed ethnicity subjects are required to validate our findings.
细胞周期蛋白依赖性激酶抑制剂 2A/B(CDKN2A/B)位于染色体特定位置,在β细胞功能和再生中具有重要作用,因此被认为是 2 型糖尿病(T2D)的候选基因。然而,迄今为止的研究报告 T2D 与 CDKN2A/B 之间的相关性存在不一致的结果。为了阐明这种不一致性,我们基于 CDKN2A/B 中 rs10811661 和 rs564398 的等位基因和基因型频率进行了荟萃分析。系统检索了 2006 年 1 月至 2010 年 11 月间发表的基于 PubMed、EMBASE 和 Medline 数据库的研究。共收集了 35 份报告,其中只有 16 项研究(包括 24407 例病例和 33937 例对照)符合纳入标准,并进行了统计学检验。对已发表数据的荟萃分析结果表明,CDKN2A/B 的 rs10811661 T 等位基因(OR 1.28,95%CI 1.21-1.36,P < 1 × 10(-5))和 TT 基因型(OR 1.32,95%CI 1.22-1.43,P < 1 × 10(-5))与 2 型糖尿病有关,但 rs564398 无关(仅等位基因:OR 0.96,95%CI 0.88-1.05,P = 0.35)。rs10811661 T 等位基因与 T2D 的相关性在亚洲人群(P < 1 × 10(-4))和欧洲人群中(P = 0.002)均观察到。本荟萃分析的结果表明,CDKN2A/B 的 rs10811661 等位基因增加了 T2D 的发病风险。需要进行更大规模的、具有混合种族人群的研究来验证我们的发现。