Fracture, bone mineral density, and the effects of calcitonin receptor gene in postmenopausal Koreans
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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).
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.
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).
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).
These results indicate that the CALCR gene may regulate bone metabolism, and +60644C > T in the CALCR gene may genetically modulate bone phenotype.
KeywordsBone mineral density CALCR Fracture SNP Postmenopause
- 3.Fogarty P, O'Beirne B, Casey C (2005) Epidemiology of the most frequent diseases in the European a-symptomatic post-menopausal women. Is there any difference between Ireland and the rest of Europe? Maturitas 52 Suppl 1:S3-S6Google Scholar
- 5.North American Menopause Society (2002) Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Menopause 9:84–101Google Scholar
- 22.Davey RA, Turner AG, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Ma C, Glatt V, MacLean HE, Vincent C, Bouxsein M, Morris HA, Findlay DM, Zajac JD (2008) Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. J Bone Miner Res 23:1182–1193CrossRefPubMedGoogle Scholar
- 23.Masi L, Becherini L, Colli E, Gennari L, Mansani R, Falchetti A, Becorpi AM, Cepollaro C, Gonnelli S, Tanini A, Brandi ML (1998) Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women. Genetics of osteoporosis. Biochem Biophys Res Commun 248:190–195CrossRefPubMedGoogle Scholar
- 28.Jo JM, Kim JS, Kim GS, Kim SW, Shin JW, Moon DH, Lee HK (1999) Cross-calibration of bone mineral density between two different dual X-ray absorptiometry systems: hologic QDR 4500-A and lunar EXPERT-XL. Kor J Nucl Med 33:282–288Google Scholar
- 33.Oliphant A, Barker DL, Stuelpnagel JR, Chee MS (2002) BeadArray technology: enabling an accurate, cost-effective approach to high-throughput genotyping. Biotechniques Suppl 56-8:60–61Google Scholar