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Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans

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  • Kristoffer Sølvsten Burgdorf
  • 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

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.

Suggested Citation

  • Kristoffer Sølvsten Burgdorf & Niels Grarup & Johanne Marie Justesen & Marie Neergaard Harder & Daniel Rinse Witte & Torben Jørgensen & Annelli Sandbæk & Torsten Lauritzen & Sten Madsbad & Torben Hans, 2011. "Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-6, January.
    • Handle: RePEc:plo:pone00:0015813
    DOI: 10.1371/journal.pone.0015813
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    1. Andrea Ventura & David G. Kirsch & Margaret E. McLaughlin & David A. Tuveson & Jan Grimm & Laura Lintault & Jamie Newman & Elizabeth E. Reczek & Ralph Weissleder & Tyler Jacks, 2007. "Restoration of p53 function leads to tumour regression in vivo," Nature, Nature, vol. 445(7128), pages 661-665, February.
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