Abstract

Previous investigations indicated that glucagon-like peptide-1 (GLP-1) played important roles in bone turnover via GLP-1 receptors (GLP1Rs) in postmenopausal state. Furthermore, polymorphisms in GLP1R gene were suggested to affect the function of GLP1Rs and be associated with many diseases. However, the relationships between GLP1R polymorphisms and osteoporosis susceptibility and bone strength remain unexplored. To address this issue, a total of 458 Chinese Han postmenopausal women were included in this study. The bone mineral density (BMD) in the lumbar spine (L₂-L₄) and femoral neck was measured by dual-energy X-ray absorptiometry (DEXA).  A missense mutation (rs1042044) in GLP1R was genotyped using allele specific TaqMan probes.  Our data showed that genetic variants of rs1042044 were significantly associated with osteoporosis (P = 0.003) and that the C allele of rs1042044 was a protective factor against osteoporosis compared to the A allele with gene dosage-dependent manner (OR, 0.579; 95% CI, 0.366 to 0.916 for AC genotype and OR, 0.404; 95% CI, 0.238 to 0.688 for CC genotype). These findings indicate that polymorphisms in GLP1R gene may affect BMD and development of osteoporosis in Chinese Han postmenopausal women, which provide novel insight into the mechanisms of osteoporosis development and target for personal prevention and treatment of osteoporosis. 

Key words: Glucagon-like peptide-1 receptor, single nucleotide polymorphism, osteoporosis, bone mineral density.

Abbreviation

BMI, Body mass index; BMD, bone mineral density; CI, confidence interval; GLP-1, glucagon-like peptide-1; GLP1R, glucagon-like peptide-1 receptor; HWE, Hardy–Weinberg Equilibrium; ORs, odds ratios; SNP, single nucleotide polymorphism.