Genetic analysis of recently identified osteoporosis susceptibility genes in southern Chinese

Abstract

Context: Fifty-six genomic loci recently were identified as associated with bone mineral density (BMD) in a large meta-analysis study of mainly European-descent subjects. Circulating factors related to calcium and phosphate metabolism, eg, serum levels of calcium, phosphate, vitamin D metabolites, PTH, and alkaline phosphatase (ALP), may affect bone turnover and metabolism. Objective and Design: We aimed to investigate the effects of these reported variants, as well as their interactions with 5 studied circulating factors, on BMD in a southern Chinese prospective cohort (n=2670). The identified interactions were further replicated in an independent cohort of 800 Chinese females. Results: Approximately half (n = 27) of the reported variants were successfully replicated in our sample of southern Chinese individuals. We further demonstrated a significant interaction betweenMARK3and serum ALP levels (Pmeta=9.89×10-6); the effect ofMARK3rs11623869 onBMD was stronger in the presence of high serum levels of ALP. In addition, several interactions between other genes and circulating factors were suggested. Conclusions: Our study has provided an independent replication of associations between several reported loci andBMDin a large sample of southern Chinese individuals. These replicated loci may represent osteoporosis susceptibility genes in both Chinese and European-descent populations. Furthermore, we have shown that serum ALP levels modified the association of MARK3 with BMD. Understanding the mechanisms of the interactions between BMD-related loci and circulating factors may help to determine the pathogenesis of susceptibility to osteoporosis and could have implications for clinical care. Copyright © 2013 by The Endocrine Society.