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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

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 replicat...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024396/
https://www.ncbi.nlm.nih.gov/pubmed/21283750
http://dx.doi.org/10.1371/journal.pone.0015813
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author 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
author_facet 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
author_sort Burgdorf, Kristoffer Sølvsten
collection PubMed
description 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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spelling pubmed-30243962011-01-31 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 Pedersen, Oluf PLoS One Research Article 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. Public Library of Science 2011-01-20 /pmc/articles/PMC3024396/ /pubmed/21283750 http://dx.doi.org/10.1371/journal.pone.0015813 Text en Burgdorf et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title_full Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title_fullStr Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title_full_unstemmed Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title_short Studies of the Association of Arg72Pro of Tumor Suppressor Protein p53 with Type 2 Diabetes in a Combined Analysis of 55,521 Europeans
title_sort studies of the association of arg72pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 europeans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024396/
https://www.ncbi.nlm.nih.gov/pubmed/21283750
http://dx.doi.org/10.1371/journal.pone.0015813
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