BoneKEy Reports | BoneKEy Watch
Evidence mounts that MPP7 is a susceptibility gene for osteoporosis
DOI:10.1038/bonekey.2012.38
MPP7 was implicated in osteoporosis risk in a previous genome-wide association study (GWAS) in a population from Hong Kong. The association of MPP7 with bone mineral density (BMD) has now been confirmed in three independent cohorts of people of Asian descent using different sampling and genotyping methods. Association of the top single nucleotide polymorphism of MPP7 (rs4317882) reached genome-wide significance in a meta-analysis of all available subjects (pmeta=4.58×10−8, n=4204).
It is not yet clear whether this genetic association is limited to the Chinese population; the need for follow-up studies in other ethnic groups was highlighted.
Xiao et al. also explored the functional significance of the MPP7 gene using human bone-derived cells and a zebrafish model. The in vitro studies showed that MPP7 was expressed in the cultured human cells during osteogenesis. In vivo studies demonstrated that MPP7 knockdown zebrafish had a lower vertebral bone mass.
Editor's comment: This paper provides functional validation for the gene MPP7, which was pinpointed in the GWAS done by Annie Kung's group. Xiao et al. replicated the top SNP rs4317882 in three additional samples (n=2684) with a meta-analysis P=4.58×10−8. The gene, coding for a membrane protein, is expressed in human bone-derived cells during osteogenesis, and seems to be localized in the osteoblastic plasma membrane.
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