title: Allelic determinants of vitamin d insufficiency, bone mineral density, and bone fractures.
abstract: BACKGROUND
  Low 25-hydroxycholecalciferol [25(OH) vitamin D] status is known to play an important role in many diseases with focus on bone health.
  
  
  OBJECTIVE
  Based on recently reported genetic determinants of vitamin D insufficiency, we aimed to analyze genetic variants of group-specific component (GC), 7-dehydrocholesterol reductase (DHCR7), and cytochrome P450IIR-1 (CYP2R1) for association with vitamin D levels, bone mineral density (BMD), and bone fractures.
  
  
  METHODS
  We conducted a cross-sectional BMD and fracture study and a prospective cohort study.
  
  
  METHODS
  The cross-sectional study comprised participants of a BMD screening study, and the prospective cohort study comprised nursing home subjects.
  
  
  METHODS
  The cross-sectional study included 342 subjects (mean age, 55.3 ± 12.0 yr), and the prospective study included 1093 subjects (mean age, 84.0 ± 6.0 yr).
  
  
  METHODS
  Patients were stratified by GC, DHCR7, and CYP2R1 genotypes. For each gene, the allele associated with lower 25(OH) vitamin D levels was designated as "risk allele." The potential role of these risk alleles in fracture risk was analyzed by logistic regression analysis including age and sex as confounders.
  
  
  METHODS
  We measured BMD and fractures.
  
  
  RESULTS
  GC genotypes were significantly associated with lower mean 25(OH) vitamin D levels in both cohorts (P = 0.001 and P = 0.048, respectively). There was no significant association of BMD with any of the genotypes. None of the alleles was associated with past fractures, whereas the DHCR7 G-allele was significantly associated with prospective fractures (odds ratio, 0.68; 95% confidence interval, 0.51-0.92; P = 0.011).
  
  
  CONCLUSIONS
  The DHCR7 gene polymorphism may be a predictor for fracture risk.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
authors.forename: Olivia
authors.initials: O
authors.lastname: Trummer
authors.forename: Verena
authors.initials: V
authors.lastname: Schwetz
authors.forename: Daniela
authors.initials: D
authors.lastname: Walter-Finell
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lerchbaum
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Markus
authors.initials: M
authors.lastname: Gugatschka
authors.forename: Harald
authors.initials: H
authors.lastname: Dobnig
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000483:Alleles; D001317:Austria / Q000453:epidemiology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D050723:Fractures, Bone / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult