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<sub>con</sub>) 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 o...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/15/7/1150 |
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| Summary: | In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBG<sub>con</sub>) 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<sub>con</sub> (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<sub>ints</sub>) were taken into account during the “deep study” of the functionality of seven important UF loci and 115 strongly linked [r<sup>2</sup> ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBG<sub>con</sub>-related SNPs correlated with UF risk: rs3779195 [T/A] <i>BAIAP2L1</i> (OR<sub>AA</sub> = 0.38; 95%CI<sub>AA</sub> = 0.20–0.91; p<sub>perm(AA)</sub> = 0.023) and rs440837 [A/G] <i>ZBTB10</i> (OR<sub>GG</sub> = 1.93; 95%CI<sub>GG</sub> = 1.17–3.14; p<sub>perm(GG)</sub> = 0.010). At the same time, seven SHBG<sub>con</sub>-related SNPs interacting with each other (four models of such SNP-SNP<sub>ints</sub> [p<sub>perm</sub> ≤ 0.01)] were found to influence UF risk. These SHBG<sub>con</sub>-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<sub>con</sub>-related genetic determinants of UF risk. |
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| ISSN: | 2075-1729 |