{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:48:13Z","timestamp":1788281293472,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["075-15-2025-529"],"award-info":[{"award-number":["075-15-2025-529"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a multifactorial disease, the pathogenesis of which is caused by a complex interaction of genetic, hormonal, and metabolic factors. The challenges of early diagnosis highlight the need to identify genetic predictors to prevent bone mineral density (BMD) loss. Given the critical role of G-protein-coupled receptors (GPCRs) in bone development and remodeling, we investigated osteoporosis-associated single-nucleotide polymorphisms (SNPs) within GPCR genes using next-generation sequencing of patient cohorts. Subsequent screening via Sanger sequencing identified three SNPs for further analysis: rs1991517 in the thyroid-stimulating hormone receptor gene (TSHR), rs6166 in the follicle-stimulating hormone receptor gene (FSHR), and rs1042713 in the \u03b22-adrenergic receptor gene (ADRB2). Our results reveal a significant association between osteoporosis and a specific homozygous genotype combination (TSHR rs1991517 CC, FSHR rs6166 AA, and ADRB2 rs1042713 AA). The functional impairment in osteodifferentiation was further validated in patient-derived cell lines harboring this triple-SNP combination. Thus, this study is the first to identify a specific combination of GPCR gene polymorphisms that may serve as a predictive biomarker for osteoporosis in early genetic screening.<\/jats:p>","DOI":"10.3390\/ijms262211117","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T15:38:09Z","timestamp":1763393889000},"page":"11117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel SNP Combination for Predictive Osteoporotic Diagnosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7825-273X","authenticated-orcid":false,"given":"Julia V.","family":"Sopova","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"},{"name":"Center for Transgenesis and Genome Editing, Saint-Petersburg State University, St. Petersburg 199034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga A.","family":"Krasnova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"},{"name":"Center of Genetic Reprogramming and Gene Therapy, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina I.","family":"Semenova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia D.","family":"Kryukova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giomar V.","family":"Vasileva","sequence":"additional","affiliation":[{"name":"Institute of Applied Computer Science, ITMO University, St. Petersburg 197101, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-9533","authenticated-orcid":false,"given":"Anna S.","family":"Zhuk","sequence":"additional","affiliation":[{"name":"Institute of Applied Computer Science, ITMO University, St. Petersburg 197101, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-0614","authenticated-orcid":false,"given":"Olga M.","family":"Lesnyak","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, North-Western State Medical University Named After I.I. Mechnikov, St. Petersburg 195298, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy V.","family":"Karelkin","sequence":"additional","affiliation":[{"name":"Traumatology and Orthopedics Department, Vreden National Medical Research Center of Traumatology and Orthopedics, St. Petersburg 195427, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina E.","family":"Neganova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"},{"name":"Center of Genetic Reprogramming and Gene Therapy, Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.2147\/TCRM.S138000","article-title":"A comprehensive overview on osteoporosis and its risk factors","volume":"14","author":"Pouresmaeili","year":"2018","journal-title":"Ther. 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