Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism.

Methodology: 212 young (<45 years) non-diabetic obese (BMI ≥ 30 kg/m²) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal (n = 55, TT > 3.5 ng/mL and FT ≥ 70 pg/mL; EuG), normal FT hypogonadism (n = 40, TT < 3.5 and FT ≥ 70 pg/mL; normal FT HG) and hypogonadism (n = 117, TT < 3.5 ng/mL and TL < 70 pg/mL; HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem).

Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) β = 3.28; (AA) β = 12.45) and a decreased of FT levels ((GA) β = -9.19; (AA) β = -18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54).

Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.