To investigate the impact of single nucleotide polymorphisms (SNPs) of SHBG gene the neighboring genes on SHBG levels, bone mineral density (BMD) and osteoporosis in Chinese males. A group of Chinese men, aged ⩾ 45 years were included in the analysis. BMD was measured with dual-energy X-ray absorptiometry (DXA), SHBG and total testosterone (TT) was measured using chemiluminescent immunoassay, and free testosterone (FT) was calculated. SNPs of SHBG gene and the neighboring genes were studied by means of improved multiple ligase detection reaction (iMLDR). A total of 404 men were included in our study. In the single locus analysis, significant associations were found between SHBG levels and four polymorphisms (rs11078701, rs9901675, rs9898876 and rs2541012) in age- and BMI-adjusted models. In addition, statistically significant difference was found between osteoporosis patients and control subjects in genotype distributions of rs9898876, rs2541012, rs6259 and rs3853894. In the models with or without adjustment for confounders (age, BMI, SHBG and free testosterone (FT) levels), carriers of variant genotype of rs9898876, rs2541012 and rs6259 had lower BMD and were more likely to suffer from osteoporosis, as compare to carriers of common genotype. Subjects with variant genotype of rs3853894 had higher BMD and were less likely to suffer from osteoporosis, as compared to subjects with common genotype. In the haplotypes analysis, CCGGT (constituted by rs11078701C, rs1017163C, rs9898876G, rs62059836G and rs2541012T) and haplotype CGGT (constituted by rs858521C, rs858518G, rs6259G and rs727428T) was associated with a significant risk effect for osteoporosis. Polymorphisms of SHBG or the neighboring genes were associated with SHBG levels or BMD and osteoporosis, suggesting the involvement of genetic variation of SHBG in bone health.
Keywords: Bone mineral density; Chinese male; Gene polymorphism; Osteoporosis; Sex hormone-binding globulin.
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