title: Genetic analysis of recently identified osteoporosis susceptibility genes in southern Chinese.
abstract: BACKGROUND
  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
  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 between MARK3 and serum ALP levels (Pmeta = 9.89 ×10(-6)); the effect of MARK3 rs11623869 on BMD 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 and BMD in 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.
authors.affiliation: MD, Department of Medicine, Faculty of Medicine, The University of Hong Kong, Hong Kong, China. kcbtan@hku.hk.
authors.forename: Su-Mei
authors.initials: SM
authors.lastname: Xiao
authors.forename: Annie W C
authors.initials: AW
authors.lastname: Kung
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.forename: Kathryn C B
authors.initials: KC
authors.lastname: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data*; D015519:Bone Density / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology* / Q000235:genetics; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases; D000469:Alkaline Phosphatase