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APC gene copy number significantly associated with bone mineral density in humans


Studies into genetic variability between individuals with osteoporosis have focused on single nucleotide polymorphisms; in this study Chew et al. also consider copy number variations (CNVs), which are insertions or deletions of larger stretches of DNA, sometimes comprising whole genes. They investigated CNVs relevant to the gene that encodes the tumor suppressor APC to find out whether there was any association with bone mineral density (BMD) variations.

DNA samples were obtained from 2070 men and women, with an average age of 47 and all Caucasian. CNV analysis was performed and compared with measurements of BMD at the spine, forearm and total hip in individual subjects. People with only one copy of the APC gene showed 13.10, 7.95 and 13.36% greater BMD at the spine, forearm and total hip, respectively, when compared with people who had the usual two copies. This, the authors suggest, shows that the APC gene, which is a known antagonist of Wnt signaling, could be an important negative regulator of bone mass and BMD.

Editor’s comment: Interestingly, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean BMD than age- and sex-matched controls, suggesting a potentially pleiotropic function of this gene.

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