Contribution of a common variant in the promoter of the 1-α-hydroxylase gene (CYP27B1) to fracture risk in the elderly

Publication Type:
Journal Article
Calcified Tissue International, 2011, 88 (2), pp. 109 - 116
Issue Date:
Filename Description Size
Thumbnail2013005863OK.pdf240.31 kB
Adobe PDF
Full metadata record
CYP27B1 encodes mitochondrial 1α-hydroxylase, which converts 25-hydroxyvitamin D to its active 1,25-dihydroxylated metabolite. We tested the hypothesis that common variants in the CYP27B1 promoter are associated with fracture risk. The study was designed as a populationbased genetic association study, which involved 153 men and 596 women aged 65-101 years, who had been followed for 2.2 years (range 0.1-5.5) between 1999 and 2006. During the follow-up period, the incidence of fragility fractures was ascertained. Bone ultrasound attenuation (BUA) was measured in all individuals, as were serum 25-hydroxyvitamin D and PTH concentrations; 86% subjects had vitamin D insufficiency. Genotypes were determined for the-1260C>A (rs10877012) and +2838T>C (rs4646536) CYP27B1 polymorphisms. A reportergene assay was used to assess functional expression of the-1260C>A CYP27B1 variants. The association between genotypes and fracture risk was analyzed by Cox's proportional hazards model. We found that genotypic distribution of CYP27B1-1260 and CYP27B1 + 2838 polymorphisms was consistent with the Hardy-Weinberg equilibrium law. The two polymorphisms were in high linkage disequilibrium, with D'= 0.96 and r 2 = 0.94. Each C allele of the CYP27B1-1260 polymorphism was associated with increased risk of fracture (hazard ratio = 1.34, 95% CI 1.03-1.73), after adjustment for age, sex, number of falls, and BUA. In transient transfection studies, a reporter gene downstream of the-1260(A)-containing promoter was more highly expressed than that containing the C allele. These data suggest that a common but functional variation within the CYP27B1 promoter gene is associated with fracture risk in the elderly. © The Author(s) 2010.
Please use this identifier to cite or link to this item: