TY  - JOUR
PY  - 2011//
TI  - Contribution of a Common Variant in the Promoter of the 1-α-Hydroxylase Gene (CYP27B1) to Fracture Risk in the Elderly
JO  - Calcified tissue international
A1  - Clifton-Bligh, Roderick J.
A1  - Nguyen, Tuan V.
A1  - Au, Amy
A1  - Bullock, Martyn
A1  - Cameron, Ian D.
A1  - Cumming, Robert
A1  - Chen, Jian Sheng
A1  - March, Lyn M.
A1  - Seibel, Markus J.
A1  - Sambrook, Philip N.
SP  - 109
EP  - 116
VL  - 88
IS  - 2
N2  - 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>
LA  - en
SN  - 0171-967X
UR  - http://dx.doi.org/10.1007/s00223-010-9434-4
ID  - ref1
ER  -