Association of rs9939609 polymorphism in the FTO gene with features of androgen status in men

The purpose of the study was to investigate the association of carriage of rs9939609 polymorphism in the FTO gene with features of androgen status in men.

Material and methods. The observational one-stage examination of 139 male patients aged 22 to 69 years, admitted to a therapeutic hospital in a planned manner has been carried out in the Clinic of the Federal Research Center for Fundamental and Translational Medicine in the period 2020–2021. All fasting men in the morning (8:00–8:30) were carried out of an anthropometric examination to determine physical development, sampling of venous blood from the cubital vein to assess the hormonal parameters of androgen status, and taking a sample of the buccal epithelium for molecular genetic research. Based on the carriage of the rs9939609 (T>A) polymorphism of the FTO gene, the following groups (G) of patients were distinguished: G1 – wild-type homozygotes (WT/WT), G2 – heterozygotes (WT/A), G3 – homozygotes for the mutant allele (A/A).

Results and discussion. The statistically significant differences were found in the levels of total testosterone between G1 and G3 (11.6 vs 14.5 nmol/L, p = 0.010), as well as free testosterone in G1 compared to G2 (0.233 vs 0.287 nmol/L, p = 0.012) and G3 (0.233 vs 0.321 nmol/L, p = 0.002) when analyzing the clinical-anthropometric and hormonal features of the androgen status of the examined male patients in the selected groups. Assessment of the association revealed statistically significant positive correlations between the carriage of the mutant allele and the levels of total (r = 0.247; p = 0.013) and free (r = 0.296; p = 0.003) testosterone, and negative - with the frequency of androgen deficiency according to the free testosterone criteria (r = –0.240; p = 0.016).

Conclusions. It has been shown that the carriage of the A/A genotype of rs9939609 polymorphism of the FTO gene is associated with an increase in the levels of total and free testosterone, that indicates a protective effect against the development of androgen deficiency in men. The obtained results suggest that this effect is due to the epigenetic effect of the FTO gene protein product on the expression of other genes involved in the synthesis of androgens in the gonads, but also in the adrenal cortex since no association of the carriage of the rs9939609 polymorphism of the FTO gene with the DHEA-C level was found.

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