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

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

doi:10.1371/journal.pone.0015813

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

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

37 Citations (Scopus)

Abstract

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 language	English
Journal	P L o S One
Volume	6
Issue number	1
Pages (from-to)	e15813
Number of pages	6
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0015813
Publication status	Published - 2011

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0015813

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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, & Pedersen, O. (2011). Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans. P L o S One, 6(1), e15813. https://doi.org/10.1371/journal.pone.0015813

Burgdorf, KS, Grarup, N , Justesen, JM, Harder, MN, Witte, DR, Jørgensen, T, Sandbæk, A, Lauritzen, T, Madsbad, S , Hansen, T, DIAGRAM Consortium & Pedersen, O 2011, 'Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans', P L o S One, vol. 6, no. 1, pp. e15813. https://doi.org/10.1371/journal.pone.0015813

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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 = "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.",

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

author = "Burgdorf, {Kristoffer S{\o}lvsten} and Niels Grarup and Justesen, {Johanne Marie} and Harder, {Marie Neergaard} and Witte, {Daniel Rinse} and Torben J{\o}rgensen and Annelli Sandb{\ae}k and Torsten Lauritzen and Sten Madsbad and Torben Hansen and {DIAGRAM Consortium} and Oluf Pedersen",

year = "2011",

doi = "10.1371/journal.pone.0015813",

language = "English",

volume = "6",

pages = "e15813",

journal = "PLoS Computational Biology",

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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

SN - 1932-6203

VL - 6

SP - e15813

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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