Vitamin D receptor polymorphisms, bone ultrasound and mineral density in post-menopausal women

Bone structure, geometry and mineral content represent complex traits with a significant heritable component. However, the specific contributing genes have not been unambiguously identified. The aim of the present cross-sectional study was to analyse an association between heel ultrasound measurements, partly reflecting bone quality, and VDR (Vitamin D receptor) gene polymorphisms in post-menopausal women, and to assess whether these associations differ from those of bone density or not.

BUA (broadband ultrasound attenuation, dB/MHz) at the right heel and BMD (bone mineral density, g/cm2) at the lumbar spine and hip were measured in 114 post-menopausal women of Caucasian origin (62.4 +/- 9.8 years). All probands were genotyped for common VDR polymorphisms--FokI, BsmI, Apal and TaqI--by restriction analysis of the PCR product.

ANCOVA revealed significant associations between calcaneal BUA adjusted for BMI (body mass index) and YSM (years since menopause), and BsmI, Apal and TaqI genotypes in the VDR gene (p < 0.02; p < 0.0003; p < 0.02 ANCOVA, respectively). BMI- and YSM-adjusted BMD was significantly associated with Fokl genotypes in the VDR gene (p < 0.028 at lumbar spine, p < 0.007 at hip).

The present data show that post-menopausal BMD and BUA are determined by different polymorphisms within the VDR gene. Non-coding polymorphisms in the 3' end of the VDR gene (BsmI, Apal, TaqI) are related to heel ultrasound while the FokI polymorphism in exon 2, located at the opposite site of the VDR gene, is associated with BMD measurements. Further studies are required to determine whether different polymorphic markers within a single gene independently determine various components of post-menopausal bone.