title: Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans.
authors.affiliation: Hagedorn Research Institute, Copenhagen, Denmark. krek@hagedorn.dk
authors.forename: Kristoffer Sølvsten
authors.initials: KS
authors.lastname: Burgdorf
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.forename: Johanne Marie
authors.initials: JM
authors.lastname: Justesen
authors.forename: Marie Neergaard
authors.initials: MN
authors.lastname: Harder
authors.forename: Daniel Rinse
authors.initials: DR
authors.lastname: Witte
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Annelli
authors.initials: A
authors.lastname: Sandbæk
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritzen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005060:Europe; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53