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

• Published in: PloS one Vol. 6; no. 1; p. e15813
• Main Authors: Burgdorf, Kristoffer Sølvsten, Grarup, Niels, Justesen, Johanne Marie, Harder, Marie Neergaard, Witte, Daniel Rinse, Jørgensen, Torben, Sandbæk, Annelli, Lauritzen, Torsten, Madsbad, Sten, Hansen, Torben, Pedersen, Oluf
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.01.2011; Public Library of Science (PLoS)
• Subjects: Alleles; Biology; Body measurements; Brain cancer; Case-Control Studies; Consortia; Control data (computers); Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes therapy; Disease prevention; DNA methylation; Europe; European Continental Ancestry Group - genetics; Europeans; Genes; Genetic aspects; Genome-Wide Association Study; Genomes; Genotype; Genotyping; Glucose; Glycoproteins; Health risk assessment; Health risks; Health sciences; Homeostasis; Hospitals; Humans; Insulin resistance; Lung cancer; Medicine; Meta-analysis; Methods; Middle age; Mutation; p53 Protein; Public health; Studies; Tumor proteins; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor suppressor proteins; Tumors; Type 2 diabetes; Europe; Denmark; Aarhus Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0015813

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. 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. 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. The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans.