Version 1
: Received: 24 July 2024 / Approved: 24 July 2024 / Online: 25 July 2024 (12:56:43 CEST)
How to cite:
Greere, D.; Haydar, S.; Grigorescu, F.; Manda, D.; Voicu, G.; Lautier, C.; Poiana, C. Fine-Scale Haplotype Mapping Reveals Association of Fto Gene with Osteoporosis and Fracture Risk in Postmenopausal Women. Preprints2024, 2024071993. https://doi.org/10.20944/preprints202407.1993.v1
Greere, D.; Haydar, S.; Grigorescu, F.; Manda, D.; Voicu, G.; Lautier, C.; Poiana, C. Fine-Scale Haplotype Mapping Reveals Association of Fto Gene with Osteoporosis and Fracture Risk in Postmenopausal Women. Preprints 2024, 2024071993. https://doi.org/10.20944/preprints202407.1993.v1
Greere, D.; Haydar, S.; Grigorescu, F.; Manda, D.; Voicu, G.; Lautier, C.; Poiana, C. Fine-Scale Haplotype Mapping Reveals Association of Fto Gene with Osteoporosis and Fracture Risk in Postmenopausal Women. Preprints2024, 2024071993. https://doi.org/10.20944/preprints202407.1993.v1
APA Style
Greere, D., Haydar, S., Grigorescu, F., Manda, D., Voicu, G., Lautier, C., & Poiana, C. (2024). Fine-Scale Haplotype Mapping Reveals Association of Fto Gene with Osteoporosis and Fracture Risk in Postmenopausal Women. Preprints. https://doi.org/10.20944/preprints202407.1993.v1
Chicago/Turabian Style
Greere, D., Corinne Lautier and Catalina Poiana. 2024 "Fine-Scale Haplotype Mapping Reveals Association of Fto Gene with Osteoporosis and Fracture Risk in Postmenopausal Women" Preprints. https://doi.org/10.20944/preprints202407.1993.v1
Abstract
Introduction. The Fat Mass and Obesity-Associated (FTO) gene encodes a demethylase that modulates RNA N6-methyladenosine (m6A) playing a regulatory role in adipocyte differentiation and pathogenesis of human obesity. Methods. To understand the potential role of FTO in osteoporosis (OP) we investigated five single nucleotide variations (SNVs) in intron 1 (rs8057044, rs8050136, rs9939609, rs62033406, rs9930506) in a cohort of postmenopausal women (n = 188) from Central Europe. Genotyping was performed by allele discrimination assay while haplotypes were reconstructed in population by PHASE 2.1. Results. The rs9930506 was strongly associated with OP (P < 0.0035), supported by Bonferroni correction (P < 0.0175) and all SNVs were stronger associated with severe OP with fragility fractures. Among 17 haplotypes, two were frequent (h1 and h9) and distributed in three main haplotypes pairs (h1/h1, h1/h9, h9/h9). Pathogenic pair h1/h9 was associated with leaner phenotype, fractures and lower bone mineral density (BMD) and carried heterozygous GA of rs9930506, while protective pair h9/h9 was associated with obesity and carried AA alleles of rs9939609. Conclusions. Concordant associations with OP, fractures risk and lower BMD at all skeletal sites indicate FTO as a promising candidate for OP explaining complex relationship with obesity and offer new perspectives for the study of epigenetic regulation of bone metabolism.
Keywords
FTO; osteoporosis; SNV; gene; haplotype
Subject
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
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