Abstract
BackgroundEstrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.MethodsFour biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.ResultsAge, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p = 0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.ConclusionSome common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.
Highlights
Estrogen activity plays a critical role in bone homeostasis
Osteoporosis is a complex disease characterized by reduced bone mineral density (BMD) and a propensity for fractures that results from the interaction of genetic and environmental factors
The objective of this study was to analyze the influence of several polymorphisms of the sex hormone binding globulin (SHBG) gene on SHBG serum levels, BMD, and osteoporotic fractures several algorithms to identify sequences likely to influence gene transcription or the function of the gene product based on a number of features, such as the homology to transcription factor binding sites, the coincidence with splicing sites, or amino acid changes [14,15,16]
Summary
Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures. Osteoporosis is a complex disease characterized by reduced bone mineral density (BMD) and a propensity for fractures that results from the interaction of genetic and environmental factors. Estrogens play a critical role in bone homeostasis, and are essential for the acquisition and maintenance of bone mass. Estrogen deficiency accounts for the marked decrease in BMD when gonadal function ceases at the menopause, leading to the high incidence of osteoporotic fractures in postmenopausal women. It must be stressed that estrogens may still play a role after the menopause. The aromatization of androgenic precursors in the adipose tissue (page number not for citation purposes)
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