title: Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK; Hugh Sinclair Unit of Human Nutrition, Department of Food & Nutritional Sciences, School of Chemistry, Food & Pharmacy, University of Reading, England RG6 6AP, UK. Electronic address: v.karani@reading.ac.uk.
authors.forename: K S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Power
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK; School of Population Health, Sansom Institute for Health Research, University of South Australia; South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Hyppönen
mesh_terms: D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D006113:United Kingdom / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D049629:Waist-Hip Ratio
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 1958 British Birth cohort; 25-hydroxyvitamin D; Metabolic traits; Vitamin D receptor; Waist-hip ratio