Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk.

In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBG) and uterine fibroids (UFs). The work was performed on a sample of 1542 women (569 with UFs and 973 without UFs [control]), from whom we obtained experimental data on the distribution of nine single-nucleotide polymorphisms (SNPs) affecting the SHBG (data confirmed in genome-wide association studies [GWASs]). When searching for associations with UFs, both the independent effects of SNPs and the effects of their SNP-SNP interactions (SNP-SNP) were taken into account during the "deep study" of the functionality of seven important UF loci and 115 strongly linked [r ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBG-related SNPs correlated with UF risk: rs3779195 [T/A] (OR = 0.38; 95%CI = 0.20-0.91; p = 0.023) and rs440837 [A/G] (OR = 1.93; 95%CI = 1.17-3.14; p = 0.010). At the same time, seven SHBG-related SNPs interacting with each other (four models of such SNP-SNP [p ≤ 0.01)] were found to influence UF risk. These SHBG-related SNPs, determining susceptibility to UF, showed strong functional relevance and were involved in pathways of gene transcription regulation, interactions with hormone ligand-binding receptors, the content control of SHBG, testosterone, liver enzymes, lipids, etc. This study's results demonstrate the effect of significant SHBG-related genetic determinants of UF risk.