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

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.

The Relation of the SHBG Gene Polymorphism (rs1799941) with PCOS in a Group of Iraqi Women

“…This result agrees with a study [21] conducted on Bahraini women, which indicated that the role of SHBG as a candidate gene for PCOS has an important and effective role in the pathophysiology of PCOS. In another study, which indicated that there is a relationship between this gene and obesity for young people without diabetes, it was found that the percentage of people carrying the AA genotype is more compared to other genotypes, and the OR value of the mutant allele was (2.54) [22]. The current study demonstrated the effect of SHBG gene polymorphisms on hormone levels in women with PCOS.…”

“…The results of our current study showed that the observed number of women with PCOS with homozygous normal genotype GG is (4) and frequency (0.057), while the observed number of women with heterozygous GA genotype is (44) and frequency (0.628). As for the affected women with a homozygous genotype of the AA mutant, the observed number was (22) and the frequency (0.314), if the frequency of the G allele was (0.37), while the frequency of the A allele was (0.63).…”

The role of SHBG and LPL gene polymorphism in the development of age-related hypogonadism in overweight men: Literature review

“…This study proves that rs1799941 of the SHBG gene determines the genetic factor for hypogonadism. It indirectly promotes obesity, which will undoubtedly be of clinical interest in the correction of hypogonadism in representatives with this polymorphism in the phenotype [34].…”

Low THRB (thyroid hormone receptor beta) Promoter Methylation Levels in Peripheral Blood Leukocytes Induced By Systematic Inflammation Are Involved in Low Thyroid Hormone Function in Metabolic Syndrome

“…dehydrogenase kinase 4) in peripheral blood leukocytes (PBLs) and LPL (lipoprotein lipase) and TNF (tumor necrosis factor) in visceral adipose tissue. 4,5 Thyroid hormones (THs) have multiple effects on lipid and glucose metabolism, energy homeostasis, and they act as both insulin agonists and antagonists in different organs. 1 Blood pressure and cardiovascular mortality may be increased in hypothyroidism.…”

“…3 Changes in the methylation levels of specific genes are also associated with MetS, such as FTO (FTO alpha-ketoglutarate dependent dioxygenase), KCNJ11 (potassium inwardly rectifying channel subfamily J member 11), PPARγ(peroxisome proliferator-activated receptor gamma), and PDK4 (pyruvate dehydrogenase kinase 4) in peripheral blood leukocytes (PBLs) and LPL (lipoprotein lipase) and TNF (tumor necrosis factor) in visceral adipose tissue. 4,5…”