madman
Super Moderator
Abstract:
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.
Importantly, obesity-associated hypogonadism has been strongly associated with visceral adiposity, lean mass loss, metabolic syndrome, insulin resistance, T2D and cardiovascular disease [3,4]. Sex-hormone binding globulin (SHBG) is a protein synthesized in the liver and secreted into the blood stream where fulfills its biological function, which is the transport of sex steroids hormones. Therefore, SHBG levels emerge as one of the most critical parameters that are implied in regulating the access of these hormones to their target tissues, where it can even regulate testosterone action [5,6].
In conclusion, in this study we found that the rs1799941 polymorphism in young non-diabetic obese males with hypogonadism was related to SHBG levels and consequently could be determining the FT fraction according to the relationship present between FT and the rs1799941 polymorphism as well. Moreover, in this study we show that the SHBG rs1799941 polymorphism differed among types of obesity-related hypogonadism in young non-diabetic males and might provide discriminatory potential to identify subjects with normal FT HG. Thus, our study described a genetic factor that could be of clinical interest in the management of obesity-related hypogonadism.
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.
Importantly, obesity-associated hypogonadism has been strongly associated with visceral adiposity, lean mass loss, metabolic syndrome, insulin resistance, T2D and cardiovascular disease [3,4]. Sex-hormone binding globulin (SHBG) is a protein synthesized in the liver and secreted into the blood stream where fulfills its biological function, which is the transport of sex steroids hormones. Therefore, SHBG levels emerge as one of the most critical parameters that are implied in regulating the access of these hormones to their target tissues, where it can even regulate testosterone action [5,6].
In conclusion, in this study we found that the rs1799941 polymorphism in young non-diabetic obese males with hypogonadism was related to SHBG levels and consequently could be determining the FT fraction according to the relationship present between FT and the rs1799941 polymorphism as well. Moreover, in this study we show that the SHBG rs1799941 polymorphism differed among types of obesity-related hypogonadism in young non-diabetic males and might provide discriminatory potential to identify subjects with normal FT HG. Thus, our study described a genetic factor that could be of clinical interest in the management of obesity-related hypogonadism.
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