@article{ref1,
title="Contribution of a Common Variant in the Promoter of the 1-α-Hydroxylase Gene (CYP27B1) to Fracture Risk in the Elderly",
journal="Calcified tissue international",
year="2011",
author="Clifton-Bligh, Roderick J. and Nguyen, Tuan V. and Au, Amy and Bullock, Martyn and Cameron, Ian D. and Cumming, Robert and Chen, Jian Sheng and March, Lyn M. and Seibel, Markus J. and Sambrook, Philip N.",
volume="88",
number="2",
pages="109-116",
abstract="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 population-based 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 reporter gene 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.<p /> <p>Language: en</p>",
language="en",
issn="0171-967X",
doi="10.1007/s00223-010-9434-4",
url="http://dx.doi.org/10.1007/s00223-010-9434-4"
}