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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2025-07-01
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| author | Marina Ponomarenko Evgeny Reshetnikov Maria Churnosova Inna Aristova Maria Abramova Vitaly Novakov Vladimir Churnosov Alexey Polonikov Denis Plotnikov Mikhail Churnosov Irina Ponomarenko |
| author_facet | Marina Ponomarenko Evgeny Reshetnikov Maria Churnosova Inna Aristova Maria Abramova Vitaly Novakov Vladimir Churnosov Alexey Polonikov Denis Plotnikov Mikhail Churnosov Irina Ponomarenko |
| author_sort | Marina Ponomarenko |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2a65002cc3344462a490d900f3980b40 |
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| issn | 2075-1729 |
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| spelling | doaj-art-2a65002cc3344462a490d900f3980b402025-08-20T03:08:09ZengMDPI AGLife2075-17292025-07-01157115010.3390/life15071150Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid RiskMarina Ponomarenko0Evgeny Reshetnikov1Maria Churnosova2Inna Aristova3Maria Abramova4Vitaly Novakov5Vladimir Churnosov6Alexey Polonikov7Denis Plotnikov8Mikhail Churnosov9Irina Ponomarenko10Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaGenetic Epidemiology Lab, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaDepartment of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, RussiaIn 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.https://www.mdpi.com/2075-1729/15/7/1150associationsex hormone-binding globulinSNPuterine fibroids |
| spellingShingle | Marina Ponomarenko Evgeny Reshetnikov Maria Churnosova Inna Aristova Maria Abramova Vitaly Novakov Vladimir Churnosov Alexey Polonikov Denis Plotnikov Mikhail Churnosov Irina Ponomarenko Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk Life association sex hormone-binding globulin SNP uterine fibroids |
| title | Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk |
| title_full | Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk |
| title_fullStr | Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk |
| title_full_unstemmed | Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk |
| title_short | Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk |
| title_sort | genetic variants linked with the concentration of sex hormone binding globulin correlate with uterine fibroid risk |
| topic | association sex hormone-binding globulin SNP uterine fibroids |
| url | https://www.mdpi.com/2075-1729/15/7/1150 |
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