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

Research output: Contribution to journalJournal articleResearchpeer-review

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

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.
Original languageEnglish
JournalP L o S One
Volume6
Issue number1
Pages (from-to)e15813
Number of pages6
ISSN1932-6203
DOIs
Publication statusPublished - 2011

    Research areas

  • Case-Control Studies, Diabetes Mellitus, Type 2, Europe, European Continental Ancestry Group, Genome-Wide Association Study, Genotype, Humans, Tumor Suppressor Protein p53

ID: 35314794