Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

Diabetes Metab. 2014 Nov;40(5):386-9. doi: 10.1016/j.diabet.2014.01.003. Epub 2014 Feb 25.

Abstract

Aim: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study.

Methods: Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test.

Results: After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e(-24)) compared to those with either one or no major alleles (-2.3%, P≤8.201e(-07), for both) of the VDR SNP rs2239179.

Conclusion: We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.

Keywords: 1958 British Birth cohort; 25-hydroxyvitamin D; Metabolic traits; Vitamin D receptor; Waist-hip ratio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure / genetics
  • Body Mass Index
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Disease Progression
  • Female
  • Genetic Association Studies
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Middle Aged
  • Obesity / epidemiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Polymorphism, Single Nucleotide*
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism
  • United Kingdom / epidemiology
  • Vitamin D / analogs & derivatives*
  • Vitamin D / genetics
  • Vitamin D / metabolism
  • Waist-Hip Ratio

Substances

  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D