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Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study

OBJECTIVE: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D)...

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Autores principales: Jorde, Rolf, Schirmer, Henrik, Wilsgaard, Tom, Joakimsen, Ragnar Martin, Mathiesen, Ellisiv Bøgeberg, Njølstad, Inger, Løchen, Maja-Lisa, Figenschau, Yngve, Berg, Jens Petter, Svartberg, Johan, Grimnes, Guri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359337/
https://www.ncbi.nlm.nih.gov/pubmed/22649517
http://dx.doi.org/10.1371/journal.pone.0037295
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author Jorde, Rolf
Schirmer, Henrik
Wilsgaard, Tom
Joakimsen, Ragnar Martin
Mathiesen, Ellisiv Bøgeberg
Njølstad, Inger
Løchen, Maja-Lisa
Figenschau, Yngve
Berg, Jens Petter
Svartberg, Johan
Grimnes, Guri
author_facet Jorde, Rolf
Schirmer, Henrik
Wilsgaard, Tom
Joakimsen, Ragnar Martin
Mathiesen, Ellisiv Bøgeberg
Njølstad, Inger
Løchen, Maja-Lisa
Figenschau, Yngve
Berg, Jens Petter
Svartberg, Johan
Grimnes, Guri
author_sort Jorde, Rolf
collection PubMed
description OBJECTIVE: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. METHODS: DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007–2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level. RESULTS: A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05). CONCLUSION: Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01395303
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spelling pubmed-33593372012-05-30 Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study Jorde, Rolf Schirmer, Henrik Wilsgaard, Tom Joakimsen, Ragnar Martin Mathiesen, Ellisiv Bøgeberg Njølstad, Inger Løchen, Maja-Lisa Figenschau, Yngve Berg, Jens Petter Svartberg, Johan Grimnes, Guri PLoS One Research Article OBJECTIVE: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. METHODS: DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007–2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level. RESULTS: A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05). CONCLUSION: Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01395303 Public Library of Science 2012-05-23 /pmc/articles/PMC3359337/ /pubmed/22649517 http://dx.doi.org/10.1371/journal.pone.0037295 Text en Jorde 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
Jorde, Rolf
Schirmer, Henrik
Wilsgaard, Tom
Joakimsen, Ragnar Martin
Mathiesen, Ellisiv Bøgeberg
Njølstad, Inger
Løchen, Maja-Lisa
Figenschau, Yngve
Berg, Jens Petter
Svartberg, Johan
Grimnes, Guri
Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title_full Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title_fullStr Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title_full_unstemmed Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title_short Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study
title_sort polymorphisms related to the serum 25-hydroxyvitamin d level and risk of myocardial infarction, diabetes, cancer and mortality. the tromsø study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359337/
https://www.ncbi.nlm.nih.gov/pubmed/22649517
http://dx.doi.org/10.1371/journal.pone.0037295
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