Association of Adenylate Cyclase 10 (ADCY10) Polymorphisms and Bone Mineral Density in Healthy Adults

Abstract

Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. Genetic sequence variations in the adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate cyclase, have previously been reported to be associated with low spinal BMD in hypercalciuric patients. Since ADCY10 is located in the region linked to spinal BMD in our previous linkage analysis, we tested whether polymorphisms in this gene are also associated with normal BMD variation in healthy adults. Sixteen single nucleotide polymorphisms (SNPs) distributed throughout ADCY10 were genotyped in two healthy groups of American whites: 1,692 premenopausal women and 715 men. Statistical analyses were performed in the two groups to test for association between these SNPs and femoral neck and lumbar spine areal BMD. We observed significant evidence of association (p<0.01) with one SNP each in men and women. Genotypes at these SNPs accounted for less than 1% of hip BMD variation in men, but 1.5% of spinal BMD in women. However, adjacent SNPs did not corroborate the association in either males or females. In conclusion, we found a modest association between an ADCY10 polymorphism and spinal areal BMD in premenopausal white women.

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts

“…In bone, increased [HCO 3 Ϫ ] inhibits osteoclast proliferation and differentiation through sAC, as demonstrated by siRNA knockdown of sAC (37). Expression of sAC may have consquences on bone health: a polymorphism in the adenylate cyclase 10 gene has been reported to "modestly" associate with bone mineral density (40).…”

Bone disease and hypercalciuria in children

“…The gene was subsequently identified as the soluble adenylate cyclase gene, and subsequent studies disclosed a direct relationship between the number of mutations found in this gene and the severity of the defect in bone formation [22]. Recently, Ichikawa et al [23] found a modest association between this soluble adenylate cyclase polymorphism and the spinal areal BMD in premenopausal women. It is unlikely that one specific genetic mutation or polymorphism will be responsible for bone loss in children with IH.…”

The flavonol glycoside icariin promotes bone formation in growing rats by activating the cAMP signaling pathway in primary cilia of osteoblasts

“…Ϫ effect on bone volume fraction of cultured mouse calvaria was blocked by the sAC inhibitor. Reed et al (46) reported sAC was associated with low spinal BMD in hypercalciuric patients, and Ichikawa et al (47) found a modest association between sAC polymorphism and spinal areal BMD in premenopausal white women. Our findings are consistent with the above results, indicating that sAC expression is essential for bone formation and should be the early signaling event mediator in icariin-promoted bone formation.…”