{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:28:25Z","timestamp":1790126905998,"version":"4.0.1"},"reference-count":100,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00034"],"award-info":[{"award-number":["25-25-00034"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The main goal of this study was to consider the role of obesity\/overweight as a potential modifier of associations between gene single nucleotide polymorphisms (SNPs) affecting the sex hormone-binding globulin level (SHBGlevel) and uterine myoma (UM). In the two women cohorts differentiated by body mass index (BMI) (BMI \u2265 25, n = 782 [379 UM\/403 control] and BMI &lt; 25, n = 760 [190 UM\/570 control]), the association of genome-wide association studies (GWAS)-correlated SHBGlevel-tied nine loci with UM was studied by method logistic regression with a subsequent in-depth evaluation of the functionality of UM-causal loci and their strongly linked variants. BMI-conditioned differences in the associations of SHBGlevel-tied loci with UM were revealed: in the BMI &lt; 25 group, a variant rs17496332 (A\/G) PRMT6 was UM-correlated (OR = 0.70; pperm = 0.024), and in the BMI \u2265 25 cohort, a SNP rs3779195 (T\/A) BAIAP2L1 was UM-associated (OR = 1.53; pperm = 0.019). Both the UM-causal loci and their proxy SNPs have pronounced probable functionality in the organism as a whole, as well as in the liver (the SHBG synthesis place), adipose tissue, uterus, etc., thereby influencing significant processes for UM biology such as regulation of the gene transcription, embryogenesis\/development, cell proliferation\/differentiation\/apoptosis, metabolism, lipid exchange, etc. In conclusion, the results of our work demonstrated, for the first time, the essential role of obesity\/overweight as a meaningful modifier of associations between SHBGlevel-tied polymorphisms and UM.<\/jats:p>","DOI":"10.3390\/life15091459","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T14:10:19Z","timestamp":1758118219000},"page":"1459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Obesity\/Overweight as a Meaningful Modifier of Associations Between Gene Polymorphisms Affecting the Sex Hormone-Binding Globulin Content and Uterine Myoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Marina","family":"Ponomarenko","sequence":"first","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5429-6666","authenticated-orcid":false,"given":"Evgeny","family":"Reshetnikov","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-8806","authenticated-orcid":false,"given":"Maria","family":"Churnosova","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Aristova","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Abramova","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Novakov","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Churnosov","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-247X","authenticated-orcid":false,"given":"Alexey","family":"Polonikov","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"},{"name":"Department of Biology, Medical Genetics and Ecology, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-6134","authenticated-orcid":false,"given":"Mikhail","family":"Churnosov","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-0166","authenticated-orcid":false,"given":"Irina","family":"Ponomarenko","sequence":"additional","affiliation":[{"name":"Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1056\/NEJMra1209993","article-title":"Uterine fibroids","volume":"369","author":"Bulun","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1210\/endrev\/bnab039","article-title":"Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment","volume":"43","author":"Yang","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Koltsova, A.S., Efimova, O.A., and Pendina, A.A. (2023). A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065752"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/humupd\/dmw023","article-title":"Uterine fibroid management: From the present to the future","volume":"22","author":"Donnez","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/GRF.0000000000000164","article-title":"Epidemiology of uterine fibroids: From menarche to menopause","volume":"59","author":"Wise","year":"2016","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1152\/physiol.00013.2021","article-title":"Uterine Fibroids: Hiding in Plain Sight","volume":"37","author":"Stewart","year":"2022","journal-title":"Physiology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cianci, S., Gulino, F.A., Palmara, V., La Verde, M., Ronsini, C., Romeo, P., Occhipinti, S., Incognito, G.G., Capozzi, V.A., and Restaino, S. (2023). Exploring Surgical Strategies for Uterine Fibroid Treatment: A Comprehensive Review of Literature on Open and Minimally Invasive Approaches. Medicina, 60.","DOI":"10.3390\/medicina60010064"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/13645706.2018.1442349","article-title":"Robotic-assisted vs. laparoscopic and abdominal myomectomy for treatment of uterine fibroids: A meta-analysis","volume":"27","author":"Wang","year":"2018","journal-title":"Minim. Invasive Ther. Allied Technol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lou, Z., Huang, Y., Li, S., Luo, Z., Li, C., Chu, K., Zhang, T., Song, P., and Zhou, J. (2023). Global, regional, and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: An age-period-cohort analysis for the global burden of disease 2019 study. BMC Public Health, 23.","DOI":"10.1186\/s12889-023-15765-x"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0378-5122(00)00160-2","article-title":"Heritability and risk factors of uterine fibroids--the Finnish Twin Cohort study","volume":"37","author":"Luoto","year":"2000","journal-title":"Maturitas"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/aje\/kws276","article-title":"African ancestry and genetic risk for uterine leiomyomata","volume":"176","author":"Wise","year":"2012","journal-title":"Am. J. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1007\/s00439-013-1340-1","article-title":"Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans","volume":"132","author":"Edwards","year":"2013","journal-title":"Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/jhg.2015.60","article-title":"Admixture mapping of genetic variants for uterine fibroids","volume":"60","author":"Zhang","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, B., Wang, T., Jiang, J., Li, M., Ma, W., Wu, H., and Zhou, Q. (2018). Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-25792-z"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Upadhyay, S., and Dubey, P.K. (2024). Gene variants polymorphisms and uterine leiomyoma: An updated review. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1330807"},{"key":"ref_16","first-page":"1875","article-title":"Genes control the cessation of a woman\u2019s reproductive life: A twin study of hysterectomy and age at menopause","volume":"83","author":"Snieder","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0020-7292(95)02533-I","article-title":"Familial predisposition to uterine leiomyomas","volume":"51","author":"Vikhlyaeva","year":"1995","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sakai, K., Tanikawa, C., Hirasawa, A., Chiyoda, T., Yamagami, W., Kataoka, F., Susumu, N., Terao, C., Kamatani, Y., and Takahashi, A. (2020). Identification of a novel uterine leiomyoma GWAS locus in a Japanese population. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-58066-8"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1007\/s00439-017-1836-1","article-title":"A multi-stage genome-wide association study of uterine fibroids in African Americans","volume":"136","author":"Hellwege","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e37110","DOI":"10.7554\/eLife.37110","article-title":"Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability","volume":"7","author":"Kuisma","year":"2018","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1038\/s41467-018-05428-6","article-title":"Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits","volume":"9","author":"Rafnar","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.1038\/s41467-019-12536-4","article-title":"Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis","volume":"10","author":"Gallagher","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41431-019-0495-1","article-title":"GWAS of five gynecologic diseases and cross-trait analysis in Japanese","volume":"28","author":"Masuda","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/ng.805","article-title":"A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids","volume":"43","author":"Cha","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Baranov, V.S., Osinovskaya, N.S., and Yarmolinskaya, M.I. (2019). Pathogenomics of Uterine Fibroids Development. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246151"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ponomareva, L., Kobzeva, K., and Bushueva, O. (2024). GWAS-Significant Loci and Uterine Fibroids Risk: Analysis of Associations, Gene-Gene and Gene-Environmental Interactions. Front. Biosci. (Sch. Ed.), 16.","DOI":"10.31083\/j.fbs1604024"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Edwards, T.L., Giri, A., Hellwege, J.N., Hartmann, K.E., Stewart, E.A., Jeff, J.M., Bray, M.J., Pendergrass, S.A., Torstenson, E.S., and Keaton, J.M. (2019). A trans-ethnic genome-wide association study of uterine fibroids. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00511"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, S.C., Chou, Y.H., Tantoh, D.M., Hsu, S.Y., Nfor, O.N., Tyan, Y.S., and Liaw, Y.P. (2022). Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet. BMC Women\u2019s Health, 22.","DOI":"10.1186\/s12905-022-01721-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1136\/jech-2019-213364","article-title":"Association between obesity and the risk of uterine fibroids: A systematic review and meta-analysis","volume":"75","author":"Qin","year":"2021","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Venkatesh, S.S., Ferreira, T., Benonisdottir, S., Rahmioglu, N., Becker, C.M., Granne, I., Zondervan, K.T., Holmes, M.V., Lindgren, C.M., and Wittemans, L.B.L. (2022). Obesity and risk of female reproductive conditions: A Mendelian randomisation study. PLoS Med., 19.","DOI":"10.1371\/journal.pmed.1004095"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100018","DOI":"10.1016\/j.jeud.2023.100018","article-title":"Prevention of Uterine Fibroids: Molecular mechanisms and potential clinical application","volume":"1","author":"Ali","year":"2023","journal-title":"J. Endometr. Uterine Disord."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qu, Y., Chen, L., Guo, S., Liu, Y., and Wu, H. (2023). Genetic liability to multiple factors and uterine leiomyoma risk: A Mendelian randomization study. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1133260"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2016","DOI":"10.1210\/clinem\/dgae036","article-title":"Body Mass Index and Uterine Fibroid Development: A Prospective Study","volume":"109","author":"Harmon","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"\u0160i\u0161ljagi\u0107, D., Bla\u017eeti\u0107, S., Heffer, M., Vranje\u0161 Dela\u0107, M., and Muller, A. (2024). The Interplay of Uterine Health and Obesity: A Comprehensive Review. Biomedicines, 12.","DOI":"10.3390\/biomedicines12122801"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1017\/S0007114521001732","article-title":"Associations between body shape across the life course and adulthood concentrations of sex hormones in men and pre- and postmenopausal women: A multicohort study","volume":"127","author":"Chen","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Szybiak-Skora, W., Cyna, W., and Lacka, K. (2025). New Insights in the Diagnostic Potential of Sex Hormone-Binding Globulin (SHBG)-Clinical Approach. Biomedicines, 13.","DOI":"10.3390\/biomedicines13051207"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"156","DOI":"10.18413\/2658-6533-2021-7-2-0-6","article-title":"Estrogens and uterine fibroids: An integrated view","volume":"7","author":"Alsudairi","year":"2021","journal-title":"Res. Results Biomed."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ohlsson, C., Wallaschofski, H., Lunetta, K.L., Stolk, L., Perry, J.R., Koster, A., Petersen, A.K., Eriksson, J., Lehtim\u00e4ki, T., and Huhtaniemi, I.T. (2011). Genetic determinants of serum testosterone concentrations in men. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002313"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Coviello, A.D., Haring, R., Wellons, M., Vaidya, D., Lehtim\u00e4ki, T., Keildson, S., Lunetta, K.L., He, C., Fornage, M., and Lagou, V. (2012). A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002805"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Prescott, J., Thompson, D.J., Kraft, P., Chanock, S.J., Audley, T., Brown, J., Leyland, J., Folkerd, E., Doody, D., and Hankinson, S.E. (2012). Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037815"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/ejhg.2015.102","article-title":"Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes","volume":"24","author":"Ruth","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41591-020-0751-5","article-title":"Using human genetics to understand the disease impacts of testosterone in men and women","volume":"26","author":"Ruth","year":"2020","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eabf8257","DOI":"10.1126\/sciadv.abf8257","article-title":"Testosterone and socioeconomic position: Mendelian randomization in 306,248 men and women in UK Biobank","volume":"7","author":"Harrison","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"bqac020","DOI":"10.1210\/endocr\/bqac020","article-title":"Cross-ancestry Genome-wide Association Studies of Sex Hormone Concentrations in Pre- and Postmenopausal Women","volume":"163","author":"Haas","year":"2022","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.placenta.2022.09.010","article-title":"Polymorphisms of hypertension susceptibility genes as a risk factors of preeclampsia in the Caucasian population of central Russia","volume":"129","author":"Churnosov","year":"2022","journal-title":"Placenta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"374","DOI":"10.18413\/2658-6533-2024-10-3-0-4","article-title":"Assessment of the relationship between marriage and migration characteristics of the population of the Belgorod region in dynamics over 130 years","volume":"10","author":"Sergeeva","year":"2024","journal-title":"Res. Results Biomed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D877","DOI":"10.1093\/nar\/gkv1340","article-title":"HaploReg v4: Systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease","volume":"44","author":"Ward","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Novakov, V., Novakova, O., Churnosova, M., Sorokina, I., Aristova, I., Polonikov, A., Reshetnikov, E., and Churnosov, M. (2023). Intergenic Interactions of SBNO1, NFAT5 and GLT8D1 Determine the Susceptibility to Knee Osteoarthritis among Europeans of Russia. Life, 13.","DOI":"10.3390\/life13020405"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.18413\/2658-6533-2019-5-4-0-11","article-title":"Molecular genetic determinants of pre-eclampsia","volume":"5","author":"Golovchenko","year":"2019","journal-title":"Res. Results Biomed."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Golovchenko, I., Aizikovich, B., Golovchenko, O., Reshetnikov, E., Churnosova, M., Aristova, I., Ponomarenko, I., and Churnosov, M. (2022). Sex Hormone Candidate Gene Polymorphisms Are Associated with Endometriosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213691"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ivanova, T., Churnosova, M., Abramova, M., Ponomarenko, I., Reshetnikov, E., Aristova, I., Sorokina, I., and Churnosov, M. (2023). Risk Effects of rs1799945 Polymorphism of the HFE Gene and Intergenic Interactions of GWAS-Significant Loci for Arterial Hypertension in the Caucasian Population of Central Russia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098309"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ivanova, T., Churnosova, M., Abramova, M., Plotnikov, D., Ponomarenko, I., Reshetnikov, E., Aristova, I., Sorokina, I., and Churnosov, M. (2023). Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097799"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Guo, Y.F., Li, J., Chen, Y., Zhang, L.S., and Deng, H.W. (2009). A new permutation strategy of pathway-based approach for genome-wide association study. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-429"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Che, R., Jack, J.R., Motsinger-Reif, A.A., and Brown, C.C. (2014). An adaptive permutation approach for genome-wide association study: Evaluation and recommendations for use. BioData Min., 7.","DOI":"10.1186\/1756-0381-7-9"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Reshetnikova, Y., Churnosova, M., Stepanov, V., Bocharova, A., Serebrova, V., Trifonova, E., Ponomarenko, I., Sorokina, I., Efremova, O., and Orlova, V. (2023). Maternal Age at Menarche Gene Polymorphisms Are Associated with Offspring Birth Weight. Life, 13.","DOI":"10.3390\/life13071525"},{"key":"ref_57","unstructured":"Gauderman, W., and Morrison, J. (2024, November 18). QUANTO 1.1: A Computer Program for Power and Sample Size Calculations Genetic\u2013Epidemiology Studies. Available online: http:\/\/hydra.usc.edu\/gxe."},{"key":"ref_58","first-page":"6.15.1","article-title":"In Silico Functional Annotation of Genomic Variation","volume":"88","author":"Butkiewicz","year":"2016","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-1-4939-9004-7_5","article-title":"Biological Interpretation of Complex Genomic Data","volume":"1908","author":"Fisch","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"488","DOI":"10.18413\/2658-6533-2020-6-4-0-5","article-title":"Allele distribution and haploblock structure of matrix metalloproteinase gene polymorphism in patients with H. pylori-negative gastric ulcer and duodenal ulcer","volume":"6","author":"Minyaylo","year":"2020","journal-title":"Res. Results Biomed."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Pavlova, N., Demin, S., Churnosov, M., Reshetnikov, E., Aristova, I., Churnosova, M., and Ponomarenko, I. (2022). Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012638"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Reshetnikov, E., Churnosova, M., Reshetnikova, Y., Stepanov, V., Bocharova, A., Serebrova, V., Trifonova, E., Ponomarenko, I., Sorokina, I., and Efremova, O. (2024). Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052647"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ponomarenko, M., Reshetnikov, E., Churnosova, M., Aristova, I., Abramova, M., Novakov, V., Churnosov, V., Polonikov, A., Plotnikov, D., and Churnosov, M. (2025). Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk. Life, 15.","DOI":"10.3390\/life15071150"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Minyaylo, O., Ponomarenko, I., Reshetnikov, E., Dvornyk, V., and Churnosov, M. (2021). Functionally significant polymorphisms of the MMP-9 gene are associated with peptic ulcer disease in the Caucasian population of Central Russia. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-92527-y"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"GTEx Consortium (2020). The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science, 369, 1318\u20131330.","DOI":"10.1126\/science.aaz1776"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1095\/biolreprod.111.092593","article-title":"Diverse roles for sex hormone-binding globulin in reproduction","volume":"85","author":"Hammond","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-16-0070","article-title":"Plasma steroid-binding proteins: Primary gatekeepers of steroid hormone action","volume":"230","author":"Hammond","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1038\/s41588-018-0222-9","article-title":"Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program","volume":"50","author":"Klarin","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41586-021-04064-3","article-title":"The power of genetic diversity in genome-wide association studies of lipids","volume":"600","author":"Graham","year":"2021","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1007\/s00125-023-05923-6","article-title":"Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood","volume":"66","author":"Hawkes","year":"2023","journal-title":"Diabetologia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41562-023-01579-9","article-title":"Participation bias in the UK Biobank distorts genetic associations and downstream analyses","volume":"7","author":"Schoeler","year":"2023","journal-title":"Nat. Hum. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1038\/s41588-024-01868-7","article-title":"A Genomics England haplotype reference panel and imputation of UK Biobank","volume":"56","author":"Shi","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Richardson, T.G., Sanderson, E., Palmer, T.M., Ala-Korpela, M., Ference, B.A., Davey Smith, G., and Holmes, M.V. (2020). Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003062"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Richardson, T.G., Leyden, G.M., Wang, Q., Bell, J.A., Elsworth, B., Davey Smith, G., and Holmes, M.V. (2022). Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation. PLoS Biol., 20.","DOI":"10.1371\/journal.pbio.3001547"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Roshandel, D., Lu, T., Paterson, A.D., and Dash, S. (2023). Beyond apples and pears: Sex-specific genetics of body fat percentage. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1274791"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1210\/er.2017-00025","article-title":"A Reappraisal of Testosterone\u2019s Binding in Circulation: Physiological and Clinical Implications","volume":"38","author":"Goldman","year":"2017","journal-title":"Endocr. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lv, M., Yu, J., Huang, Y., Ma, J., Xiang, J., Wang, Y., Li, L., Zhang, Z., and Liao, H. (2022). Androgen Signaling in Uterine Diseases: New Insights and New Targets. Biomolecules, 12.","DOI":"10.3390\/biom12111624"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1210\/jc.2015-2935","article-title":"Circulating Sex Hormones and Risk of Uterine Fibroids: Study of Women\u2019s Health Across the Nation (SWAN)","volume":"101","author":"Wong","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wang, H., Li, C., Chen, L., Zhang, M., Ren, T., and Zhang, S. (2024). Causal relationship between female reproductive factors, sex hormones and uterine leiomyoma: A Mendelian randomization study. Reprod. Biomed. Online, 48.","DOI":"10.1016\/j.rbmo.2023.103584"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e58615","DOI":"10.7554\/eLife.58615","article-title":"GWAS of three molecular traits highlights core genes and pathways alongside a highly polygenic background","volume":"10","author":"Naqvi","year":"2021","journal-title":"eLife"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Machado-Lopez, A., Sim\u00f3n, C., and Mas, A. (2021). Molecular and Cellular Insights into the Development of Uterine Fibroids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168483"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"123345","DOI":"10.1016\/j.lfs.2024.123345","article-title":"Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities","volume":"362","author":"Ploumaki","year":"2025","journal-title":"Life Sci."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ali, M., Ciebiera, M., Vafaei, S., Alkhrait, S., Chen, H.Y., Chiang, Y.F., Huang, K.C., Feduniw, S., Hsia, S.M., and Al-Hendy, A. (2023). Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics. Cells, 12.","DOI":"10.3390\/cells12081117"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.advms.2024.01.001","article-title":"Progesterone signaling in uterine leiomyoma biology: Implications for potential targeted therapy","volume":"69","author":"Szucio","year":"2024","journal-title":"Adv. Med. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Omar, M., Laknaur, A., Al-Hendy, A., and Yang, Q. (2019). Myometrial progesterone hyper-responsiveness associated with increased risk of human uterine fibroids. BMC Women\u2019s Health, 19.","DOI":"10.1186\/s12905-019-0795-1"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mce.2011.05.044","article-title":"The role of progesterone signaling in the pathogenesis of uterine leiomyoma","volume":"358","author":"Kim","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1055\/s-0035-1558451","article-title":"Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth","volume":"33","author":"Bulun","year":"2015","journal-title":"Semin. Reprod. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jsbmb.2003.09.007","article-title":"Differential expression of Akt\/protein kinase B, Bcl-2 and Bax proteins in human leiomyoma and myometrium","volume":"87","author":"Lengyel","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1177\/0192623315621414","article-title":"Immunoexpression of Steroid Hormone Receptors and Proliferation Markers in Uterine Leiomyoma and Normal Myometrial Tissues from the Miniature Pig, Sus scrofa","volume":"44","author":"Mozzachio","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Khan, K.N., Fujishita, A., Koshiba, A., Ogawa, K., Mori, T., Ogi, H., Itoh, K., Teramukai, S., and Kitawaki, J. (2020). Expression profiles of E\/P receptors and fibrosis in GnRHa-treated and -untreated women with different uterine leiomyomas. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0242246"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/biolre\/iox094","article-title":"Selective progesterone receptor modulators for fertility preservation in women with symptomatic uterine fibroids","volume":"97","author":"Ali","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pavlova, N., Demin, S., Churnosov, M., Reshetnikov, E., Aristova, I., Churnosova, M., and Ponomarenko, I. (2022). The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102617"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Ponomarenko, I., Pasenov, K., Churnosova, M., Sorokina, I., Aristova, I., Churnosov, V., Ponomarenko, M., Reshetnikova, Y., Reshetnikov, E., and Churnosov, M. (2024). Obesity-Dependent Association of the rs10454142 PPP1R21 with Breast Cancer. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040818"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"69","DOI":"10.18413\/2658-6533-2024-10-1-0-4","article-title":"Features of associations of SHBG-related genes with breast cancer in women, depending on the presence of hereditary burden and mutations in the BRCA1\/CHEK2 genes","volume":"10","author":"Pasenov","year":"2024","journal-title":"Res. Results Biomed."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s42836-023-00229-9","article-title":"Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population","volume":"6","author":"Novakov","year":"2024","journal-title":"Arthroplasty"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Abramova, M., Churnosova, M., Efremova, O., Aristova, I., Reshetnikov, E., Polonikov, A., Churnosov, M., and Ponomarenko, I. (2022). Effects of pre-pregnancy over-weight\/obesity on the pattern of association of hypertension susceptibility genes with preeclampsia. Life, 12.","DOI":"10.3390\/life12122018"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ponomarenko, I., Pasenov, K., Churnosova, M., Sorokina, I., Aristova, I., Churnosov, V., Ponomarenko, M., Reshetnikov, E., and Churnosov, M. (2024). Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042182"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"75","DOI":"10.18413\/2658-6533-2025-11-1-0-4","article-title":"Genetic variants of sex hormone-binding globulin and hormonal profile in patients with genital endometriosis","volume":"11","author":"Ponomareva","year":"2025","journal-title":"Res. Results Biomed."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.euros.2021.04.010","article-title":"Genetic Susceptibility for Low Testosterone in Men and Its Implications in Biology and Screening: Data from the UK Biobank","volume":"29","author":"Fantus","year":"2021","journal-title":"Eur. Urol. Open Sci."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:20Z","timestamp":1760035640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/9\/1459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":100,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["life15091459"],"URL":"https:\/\/doi.org\/10.3390\/life15091459","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]}}}