Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds androgens and oestrogens, and regulates their bioavailability to target tissues. To date, several human SHBG gene polymorphisms have been identified. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, and hyperandrogenism has been considered to be a hallmark of PCOS. Many studies have examined the association between SHBG gene polymorphisms and PCOS risk, but the results have been inconclusive or inconsistent. Therefore, the aim of this meta-analysis was to investigate whether SHBG gene polymorphisms are associated with risk of PCOS. Twelve studies were included, involving 4733 participants: 2271 patients with PCOS and 2462 control participants. The results revealed that SHBG polymorphism of eight or more (TAAAA)n pentanucleotide repeats (rs35785886) was associated with PCOS risk (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.06, 1.44, Z = 2.77, P = 0.006) and low serum SHBG concentrations in women with PCOS (standardized mean difference = -0.83, 95% CI = -1.54, -0.12, Z = 2.30, P = 0.02). Other SHBG gene polymorphisms (rs6259, rs6257, rs727428 and rs1799941) were not significantly associated with either PCOS risk or serum SHBG concentrations. These findings suggest that the presence of a polymorphism of eight or more SHBG (TAAAA)_n may be a predictive factor for the risk of PCOS.