Work

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

Year: 2025

Type: article

Abstract: In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBGcon) 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 SHBGcon (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-SNPints) were taken into account during the “deep study” of the functionality of seven important UF loci and 115 strongly linked [r2 ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBGcon-related SNPs correlated with UF risk: rs3779195 [T/A] BAIAP2L1 (ORAA = 0.38; 95%CIAA = 0.20–0.91; pperm(AA) = 0.023) and rs440837 [A/G] ZBTB10 (ORGG = 1.93; 95%CIGG = 1.17–3.14; pperm(GG) = 0.010). At the same time, seven SHBGcon-related SNPs interacting with each other (four models of such SNP-SNPints [pperm ≤ 0.01)] were found to influence UF risk. These SHBGcon-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 SHBGcon-related genetic determinants of UF risk.

Source: Life

DOI: 10.3390/life15071150