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Meta-Analysis
. 2011 Jan 20;6(1):e15813.
doi: 10.1371/journal.pone.0015813.

Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans

Kristoffer Sølvsten Burgdorf  1 , Niels Grarup, Johanne Marie Justesen, Marie Neergaard Harder, Daniel Rinse Witte, Torben Jørgensen, Annelli Sandbæk, Torsten Lauritzen, Sten Madsbad, Torben Hansen; DIAGRAM Consortium; Oluf Pedersen
Affiliations
Meta-Analysis

Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans

Kristoffer Sølvsten Burgdorf et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Estimated odd ratio (95% CIs) of present and previously reported associations of the G-allele of TP53 rs1042522 with type 2 diabetes when analysed according to an additive genetic model (n = 55,521).
No heterogeneity between studies was observed (P = 0.91). Numbers in square brackets designate numbers of type 2 diabetic patients and control subjects, respectively.
See this image and copyright information in PMC

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