Ichikawa Shoji, Koller Daniel L, Curry Leah R, Lai Dongbing, Xuei Xiaoling, Edenberg Howard J, Hui Siu L, Peacock Munro, Foroud Tatiana, Econs Michael J
Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, Clinical Building 459, Indianapolis, IN 46202-5121, USA.
Calcif Tissue Int. 2009 Feb;84(2):97-102. doi: 10.1007/s00223-008-9200-z. Epub 2008 Dec 18.
Phenotypic variation in bone mineral density (BMD) among healthy adults is influenced by both genetic and environmental factors. Sequence variations in the adenylate cyclase 10 (ADCY10) gene, which is also called soluble adenylate cyclase, have previously been 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: 1692 premenopausal women and 715 men. Statistical analyses were performed in the two groups to test for association between these SNPs and the 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 <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 men or women. In conclusion, we found a modest association between an ADCY10 polymorphism and the spinal areal BMD in premenopausal white women.
健康成年人骨矿物质密度（BMD）的表型变异受遗传和环境因素的影响。腺苷酸环化酶10（ADCY10）基因（也称为可溶性腺苷酸环化酶）的序列变异先前已与高钙尿症患者的低脊柱BMD相关。由于ADCY10位于我们先前连锁分析中与脊柱BMD相关的区域，我们测试了该基因中的多态性是否也与健康成年人的正常BMD变异相关。在两组健康的美国白人中对分布于整个ADCY10的16个单核苷酸多态性（SNP）进行了基因分型：1692名绝经前女性和715名男性。在这两组中进行了统计分析，以测试这些SNP与股骨颈和腰椎骨面积密度之间的关联性。我们观察到显著的关联证据（p < 0.01），男性和女性各有一个SNP。这些SNP的基因型在男性中占髋部BMD变异的比例不到1%，但在女性中占脊柱BMD的1.5%。然而，相邻的SNP在男性或女性中均未证实这种关联。总之，我们发现ADCY10多态性与绝经前白人女性的脊柱骨面积密度之间存在适度关联。
