13 research outputs found
Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women
<p>Abstract</p> <p>Background</p> <p>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 <it>SHBG </it>gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.</p> <p>Methods</p> <p>Four biallelic polymorphisms of the <it>SHBG </it>gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.</p> <p>Results</p> <p>Age, body weight, and two polymorphisms of the <it>SHBG </it>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.</p> <p>Conclusion</p> <p>Some common genetic variants of the <it>SHBG </it>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.</p
Genetic Determinants of Serum Testosterone Concentrations in Men
Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation