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Burgdorf, K.S.* ; Grarup, N.* ; Justesen, J.M.* ; Harder, M.N.* ; Witte, D.R.* ; Jørgensen, T.* ; Sandbæk, A.* ; Lauritzen, T.* ; Madsbad, S.* ; Hansen, T.* ; DIAGRAM Consortium (Huth, C. ; Grallert, H. ; Klopp, N. ; Petersen, A.-K. ; Thorand, B. ; Illig, T. ; Meitinger, T. ; Gieger, C.) ; Pedersen, O.*

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 6:e15813 (2011)
Publ. Version/Full Text Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords BETA-CELL FUNCTION; INSULIN SENSITIVITY; CANDIDATE GENES; POLYMORPHISM; GLUCOSE; HOMEOSTASIS; POPULATION; RESISTANCE; TRAITS; CANCER
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 6, Issue: 1, Pages: , Article Number: e15813 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed