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Bone Mineral Density and Its Change in White Women: Estrogen and Vitamin D Receptor Genotypes and Their Interaction
Author(s) -
Willing Marcia,
Sowers Maryfran,
Aron David,
Clark M. K.,
Burns Trudy,
Bunten Carol,
Crutchfield Mary,
D'Agostino Danielle,
Jannausch Mary
Publication year - 1998
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.1998.13.4.695
Subject(s) - bone mineral , estrogen receptor alpha , endocrinology , medicine , estrogen , genotype , estrogen receptor , white (mutation) , calcitriol receptor , bone density , vitamin d and neurology , osteoporosis , biology , genetics , gene , cancer , breast cancer
Low bone mineral density (BMD) is a major risk factor for development of osteoporosis; increasing evidence suggests that attainment and maintenance of peak bone mass as well as bone turnover and bone loss have strong genetic determinants. We examined the association of BMD levels and their change over a 3‐year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre‐ and perimenopausal women who were part of the Michigan Bone Health Study, a population‐based longitudinal study of BMD. Body composition measurements, reproductive hormone profiles, bone‐related serum protein measurements, and life‐style characteristics were also available on each woman. Based on evaluation of women, ER genotypes (identified by Pvu II [ n = 253] and Xba I [ n = 248]) were significantly predictive of both lumbar spine ( p < 0.05) and total body BMD level, but not their change over the 3‐year period examined. The VDR Bsm I restriction fragment length polymorphism was not associated with baseline BMD, change in BMD over time, or any of the bone‐related serum and body composition measurements in the 372 women in whom it was evaluated. Likewise, none of the other polymorphic markers was associated with BMD measurements. However, we identified a significant gene × gene interaction effect ( p < 0.05) for the VDR locus and Pvu II ( p < 0.005) and Xba I ( p < 0.05) polymorphisms, which impacted BMD levels. Women who had the (−/−) Pvu II ER and bb VDR genotype combination had a very high average BMD, while individuals with the (−/−) Pvu II ER and BB VDR genotype had significantly lower BMD levels. This contrast was not explained by differences in serum levels of osteocalcin, parathyroid hormone, 1,25‐dihydroxyvitamin D, or 25‐dihydroxyvitamin D. These data suggest that genetic variation at the ER locus, singly and in relation to the vitamin D receptor gene, influences attainment and maintenance of peak bone mass in younger women, which in turn may render some individuals more susceptible to osteoporosis than others.