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

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.