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) 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).


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT01395303.
Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, and Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. rolf.jorde@unn.no
Rolf
R
Jorde
Henrik
H
Schirmer
Tom
T
Wilsgaard
Ragnar Martin
RM
Joakimsen
Ellisiv Bøgeberg
EB
Mathiesen
Inger
I
Njølstad
Maja-Lisa
ML
Løchen
Yngve
Y
Figenschau
Jens Petter
JP
Berg
Johan
J
Svartberg
Guri
G
Grimnes
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D023381:Endpoint Determination; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology*; D009369:Neoplasms / Q000097:blood / Q000453:epidemiology*; D009664:Norway / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase