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

Abstract

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.