在对 55521 名欧洲人的综合分析中，研究抑癌蛋白 p53 的 Arg72Pro 与 2 型糖尿病的关联。
Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans.
机构信息
Hagedorn Research Institute, Copenhagen, Denmark.
出版信息
PLoS One. 2011 Jan 20;6(1):e15813. doi: 10.1371/journal.pone.0015813.
AIMS
A study of 222 candidate genes in type 2 diabetes reported association of variants in RAPGEF1, ENPP1, TP53, NRF1, SLC2A2, SLC2A4 and FOXC2 with type 2 diabetes in 4,805 Finnish individuals. We aimed to replicate these associations in a Danish case-control study and to substantiate any replicated associations in meta-analyses. Furthermore, we evaluated the impact on diabetes-related intermediate traits in a population-based sample of middle-aged Danes.
METHODS
We genotyped nine lead variants in the seven genes in 4,973 glucose-tolerant and 3,612 type 2 diabetes Danish individuals. In meta-analyses we combined case-control data from the DIAGRAM+ Consortium (n = 47,117) and the present genotyping results. The quantitative trait studies involved 5,882 treatment-naive individuals from the Danish Inter99 study.
RESULTS
None of the nine investigated variants were significantly associated with type 2 diabetes in the Danish samples. However, for all nine variants the estimate of increase in type 2 diabetes risk was observed for the same allele as previously reported. In a meta-analysis of published and online data including 55,521 Europeans the G-allele of rs1042522 in TP53 showed significant association with type 2 diabetes (OR = 1.06 95% CI 1.02-1.11, p = 0.0032). No substantial associations with diabetes-related intermediary phenotypes were found.
CONCLUSION
The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans.
目的
在一项针对 222 个候选基因的研究中，报告了 RAPGEF1、ENPP1、TP53、NRF1、SLC2A2、SLC2A4 和 FOXC2 中的变体与 4805 名芬兰个体的 2 型糖尿病之间的关联。我们旨在在丹麦病例对照研究中复制这些关联，并在荟萃分析中证实任何复制的关联。此外，我们还在一个基于人群的丹麦中年人群样本中评估了这些关联对与糖尿病相关的中间表型的影响。
方法
我们对 7 个基因中的 9 个主要变体在 4973 名糖耐量正常和 3612 名 2 型糖尿病丹麦个体中进行了基因分型。在荟萃分析中，我们结合了 DIAGRAM+ 联盟（n = 47117）和当前基因分型结果的病例对照数据。在定量特征研究中，我们涉及了来自丹麦 Inter99 研究的 5882 名未经治疗的个体。
结果
在所研究的 9 个变体中，没有一个在丹麦样本中与 2 型糖尿病显著相关。然而，对于所有 9 个变体，观察到与先前报道的相同等位基因相关的 2 型糖尿病风险增加的估计。在包括 55521 名欧洲人的已发表和在线数据的荟萃分析中，TP53 中的 rs1042522 的 G 等位基因与 2 型糖尿病显著相关（OR = 1.06 95%CI 1.02-1.11，p = 0.0032）。未发现与糖尿病相关的中间表型有实质性关联。
结论
在对 55521 名欧洲人的联合分析中，TP53 rs1042522 的 G 等位基因与 2 型糖尿病的患病率增加相关。
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