Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans

Summary In a candidate gene association study, we found that the variations of calcitonin receptor (CALCR) gene were related to the risk of vertebral fracture and increased bone mineral density (BMD). Introduction Calcitonins through calcitonin receptors inhibit osteoclast-mediated bone resorption and modulate calcium ion excretion by the kidney and also prevent vertebral bone loss in early menopause. Methods To identify genetically susceptible factors of osteoporosis, we discovered the variations in CALCR gene, genotyped in Korean postmenopausal women (n = 729), and examined the potential involvement of seven single-nucleotide polymorphism (SNPs) and their haplotypes in linkage disequilibrium block (BL_hts). Results The SNPs, +43147G > C (intron 7), +60644C > T (exon13, 3' untranslated region), and their haplotypes, BL2_ht1 and BL2_ht2, showed a significant association with risk of vertebral fracture (p = 0.048-0.004) and BL2_ht1 showed a highly significant protective effect. Moreover, the polymorphism +60644C > T showed a highly significant association with BMD at both lumbar spine and femoral neck. The subjects carrying CC and CT genotypes with the SNP, +60644C > T, had higher BMD values at the lumbar spine (p = 0.01-0.001) and femoral neck (p = 0.025-0.009). Conclusion These results indicate that the CALCR gene may regulate bone metabolism, and +60644C > T in the CALCR gene may genetically modulate bone phenotype.