Association Between FTO rs1558902 Polymorphism, Age-Related Hypogonadism, and Central Obesity in Japanese Men

Obesity and low testosterone levels are closely interconnected, with the FTO gene being the most robust genetic determinant of body mass index (BMI). However, whether this primary genetic driver of obesity directly influences the hypothalamic-pituitary-testicular (HPT) axis remains unclear.

In this cross-sectional study of 251 Japanese men, we performed genotyping for the FTO rs1558902 polymorphism. Anthropometric measurements (BMI and waist-to-hip ratio [WHR]), total testosterone (tT), free testosterone (fT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were assessed. Central obesity was defined as WHR ≥ 0.9.

The FTO A-allele frequency was 35.9%. A-allele carriers had significantly higher BMI than non-carriers (p < 0.05), but no significant differences were found in tT or fT levels between genotypes. tT was inversely correlated with BMI and WHR (p < 0.01). Men with central obesity exhibited significantly lower tT and fT levels alongside elevated LH and FSH levels (p < 0.05). Multivariate analysis confirmed that the FTO genotype was not independently associated with testosterone levels.

Although the FTO rs1558902 polymorphism was associated with a higher BMI, it did not directly correlate with testosterone levels in Japanese men. This suggests that a genetic predisposition to obesity may not be a direct determinant of low testosterone levels. Instead, the observed elevation of gonadotropins in men with central obesity highlights the significant impact of age-related testicular dysfunction.