TY - JOUR

T1 - Novel SNP Combination for Predictive Osteoporotic Diagnosis

AU - Сопова, Юлия Викторовна

AU - Краснова, Ольга Александровна

AU - Семенова, Полина Игоревна

AU - Крюкова, Юлия Дмитриевна

AU - Васильева, Гиомар Владиславовна

AU - Жук, Анна Сергеевна

AU - Лесняк, Ольга Михайловна

AU - Карелкин, Виталий

AU - Неганова, Ирина Эриковна

N1 - Times Cited in Web of Science Core Collection: 0 Total Times Cited: 0 Cited Reference Count: 91

PY - 2025/11/17

Y1 - 2025/11/17

N2 - 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 beta 2-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.

AB - 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 beta 2-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.

KW - osteoporosis

KW - GPCR

KW - <italic>ADRB2</italic>

KW - <italic>FSHR</italic>

KW - <italic>TSHR</italic>

KW - polymorphism

KW - SNP combination

KW - osteodifferentiation

KW - BONE-MINERAL DENSITY

KW - SENSING RECEPTOR GENE

KW - LEPTIN RECEPTOR

KW - POLYMORPHISMS

KW - ASSOCIATION

KW - MUTATIONS

KW - FRACTURE

KW - VARIANTS

KW - AXIS

KW - RISK

U2 - 10.3390/ijms262211117

DO - 10.3390/ijms262211117

M3 - Article

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 22

ER -