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J Clin Endocrinol Metab. 2012 Jul;97(7):E1234-40. doi: 10.1210/jc.2011-3088. Epub 2012 Apr 24.

Allelic determinants of vitamin d insufficiency, bone mineral density, and bone fractures.

Author information

1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Abstract

CONTEXT:

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.

DESIGN:

We conducted a cross-sectional BMD and fracture study and a prospective cohort study.

SETTING:

The cross-sectional study comprised participants of a BMD screening study, and the prospective cohort study comprised nursing home subjects.

PATIENTS:

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).

INTERVENTIONS:

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.

MAIN OUTCOME MEASURES:

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.

PMID:
22535976
DOI:
10.1210/jc.2011-3088
[Indexed for MEDLINE]

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