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The Association Between Heel Ultrasound and Hormone Replacement Therapy Is Modulated by a Two‐Locus Vitamin D and Estrogen Receptor Genotype
Author(s) -
Giguère Yves,
Dodin Sylvie,
Blanchet Claudine,
Morgan Kenneth,
Rousseau François
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.6.1076
Subject(s) - calcitriol receptor , heel , genotype , endocrinology , medicine , estrogen , hormone replacement therapy (female to male) , vitamin d and neurology , estrogen receptor , biology , breast cancer , genetics , gene , anatomy , testosterone (patch) , cancer
Evidence supports the role of estrogen deprivation in the process of bone remodeling 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‐Canadian 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 results were expressed as an age‐ and‐weight‐adjusted stiffness index (heel SI z score). Our aim was to investigate the interaction between hormone‐replacement 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 responsible for over 30% of the total HRT‐related heel SI difference in the whole sample. Women bearing this combined VDR/ESR1 genotype who received HRT for more 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 translate into a 2‐ to 3‐fold difference in the risk of fracture. Although follow‐up studies are needed, our findings suggest that QUS of the heel in postmenopausal women taking HRT is affected by variation in VDR and ESR1 loci, jointly.