title: Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study.
abstract: BACKGROUND
  Though the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population.
  
  
  RESULTS
  Measurements and DNA were obtained from the participants in the Tromsø Study in 1994-1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05-1.49) for T2D and 1.14 (1.02-1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints.
  
  
  CONCLUSIONS
  The VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ieva
authors.initials: I
authors.lastname: Zostautiene
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jorde
authors.affiliation: Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Cardiothoracic and Respiratory Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Schirmer
authors.affiliation: Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ellisiv Bøgeberg
authors.initials: EB
authors.lastname: Mathiesen
authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Njølstad
authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Maja-Lisa
authors.initials: ML
authors.lastname: Løchen
authors.affiliation: Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Wilsgaard
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ragnar Martin
authors.initials: RM
authors.lastname: Joakimsen
authors.affiliation: Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.|Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Elena
authors.initials: E
authors.lastname: Kamycheva
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D055812:Community-Based Participatory Research; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D009664:Norway / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics*; D015996:Survival Rate
chemical_list: D018167:Receptors, Calcitriol