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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Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans. / Burgdorf, Kristoffer Sølvsten; Grarup, Niels; Justesen, Johanne Marie; Harder, Marie Neergaard; Witte, Daniel Rinse; Jørgensen, Torben; Sandbæk, Annelli; Lauritzen, Torsten; Madsbad, Sten; Hansen, Torben; DIAGRAM Consortium ; Pedersen, Oluf.
In: P L o S One, Vol. 6, No. 1, 2011, p. e15813.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
AU - Burgdorf, Kristoffer Sølvsten
AU - Grarup, Niels
AU - Justesen, Johanne Marie
AU - Harder, Marie Neergaard
AU - Witte, Daniel Rinse
AU - Jørgensen, Torben
AU - Sandbæk, Annelli
AU - Lauritzen, Torsten
AU - Madsbad, Sten
AU - Hansen, Torben
AU - DIAGRAM Consortium
AU - Pedersen, Oluf
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 2
KW - Europe
KW - European Continental Ancestry Group
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Tumor Suppressor Protein p53
U2 - 10.1371/journal.pone.0015813
DO - 10.1371/journal.pone.0015813
M3 - Journal article
C2 - 21283750
VL - 6
SP - e15813
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
ER -
ID: 35314794