The association between heel ultrasound and hormone replacement therapy ismodulated by a two-locus vitamin D and estrogen receptor genotype

Evidence supports the role of estrogen deprivation in the process of bone r emodeling and increased risk of fracture in postmenopausal women but little is known about the genetic basis of individual differences in response to therapy, In a cross-sectional study, 425 ambulatory postmenopausal French-C anadian women from Quebec (age range, 42-85 years old) were genotyped for a common Bsm I polymorphism at the vitamin D receptor (VDR) gene as well as a Pvu II polymorphism in the estrogen receptor (ESR1) gene, Heel ultrasound was determined by right calcaneal quantitative ultrasound (QUS) and result s were expressed as an age-and-weight-adjusted stiffness index (heel SI z s core). Our aim was to investigate the interaction between hormone-replaceme nt therapy (HRT) and receptor genotypes in an effect on heel SI. Notably, a two-locus genotype (VDR-bb/ESR-PP) present in 9.5 % of women was responsib le for over 30 % of the total HRT-related heel SI difference in the whole s ample. Women bearing this combined VDR/ESR1 genotype who received HRT for m ore than 5 years had a 21% (1.25 SD) greater heel SI (p = 0.002) than those bearing the same genotype but who received HRT for <5 years. This may tran slate into a 2- to 3-fold difference in the risk of fracture. Although foll ow-up studies are needed, our findings suggest that QUS of the heel in post menopausal women taking HRT is affected by variation in VDR and ESR1 loci, jointly.