Postmenopausal osteoporosis (PMOP) is a prevalent form of primary osteoporosis, affecting over 40% of postmenopausal women. Previous studies have suggested a potential association between single nucleotide polymorphisms (SNPs) in glucagon-like peptide-1 receptor (GLP-1R) and PMOP in postmenopausal Chinese women. However, available evidence remains inconclusive. Therefore, this study aimed to investigate the possible association between GLP-1R SNPs and PMOP in Han Chinese women. Thus, we conducted a case-control study with 152 postmenopausal Han Chinese women aged 45-80 years, including 76 women with osteoporosis and 76 without osteoporosis. Seven SNPs of the GLP-1R were obtained from the National Center of Biotechnology Information and Genome Variation Server. We employed three genetic models to assess the association between GLP-1R genetic variants and osteoporosis in postmenopausal women, while also investigating SNP-SNP and SNP-environment interactions with the risk of PMOP. In this study, we selected seven GLP-1R SNPs (rs1042044, rs2268641, rs10305492, rs6923761, rs1126476, rs2268657, and rs2295006). Of these, the minor allele A of rs1042044 was significantly associated with an increased risk of PMOP. Genetic model analysis revealed that individuals carrying the A allele of rs1042044 had a higher risk of developing osteoporosis in the dominant model (P = 0.029, OR = 2.76, 95%CI: 1.09-6.99). Furthermore, a multiplicative interaction was found between rs1042044 and rs2268641 that was associated with osteoporosis in postmenopausal women (Pinteraction = 0.034). Importantly, this association remained independent of age, menopausal duration, family history of osteoporosis, and body mass index. However, no significant relationship was observed between GLP-1R haplotypes and PMOP. In conclusion, this study suggests a close association between the A allele on the GLP-1R rs1042044 and an increased risk of PMOP. Furthermore, this risk was significantly augmented by an SNP-SNP interaction with rs2268641. These results provide new scientific insights into the development of personalized prevention strategies and treatment approaches for PMOP.
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