title: Genetic variants in GREM2 are associated with bone mineral density in a southern Chinese population.
abstract: BACKGROUND
  Gremlin 2 (GREM2) is a regulator of osteoblast differentiation and osteogenesis. A recent genome-wide association study identified GREM2 as a novel susceptibility gene for trabecular volumetric bone mineral density (BMD).
  
  
  OBJECTIVE
  We investigated whether GREM2 gene variants were associated with areal BMD in southern Chinese people.
  
  
  METHODS
  We genotyped 108 single-nucleotide polymorphisms (SNPs) in 417 cases (defined as BMD Z-score ≤-1.28) and 359 controls (defined as BMD Z-score ≥+1). Multivariable logistic regression using an additive model was used to evaluate the association. The most associated SNPs of BMD at the spine, femoral neck, and total hip was then replicated in an additional 454 cases and 401 controls.
  
  
  RESULTS
  Twelve, 13, and 14 SNPs showed nominal association with BMD at the spine, femoral neck, and total hip, respectively. The minor alleles of rs9728351 (odds ratio [OR] = 2.56; 95% confidence interval [CI] = 1.33-4.92), rs11588607 (OR = 1.65; 95% CI = 1.14-2.4), and rs4454537 (OR = 1.87; 95% CI = 1.22-2.86) were associated with the low BMD at the spine, femoral neck, and total hip, respectively. Among these SNPs most associated with BMD, rs4454537 was successfully replicated in an independent cohort (OR = 1.59; 95% CI = 1.05-2.4). Meta-analysis showed that the minor allele of rs4454537 was associated with low total hip BMD with an OR of 1.72 (95% CI = 1.28-2.31) (P = 3.2 × 10(-4); P(corrected) = .043).
  
  
  CONCLUSIONS
  The minor allele of rs4454537 is significantly associated with low BMD at the total hip of southern Chinese people. Our study further suggests GREM2 as a novel susceptibility gene for osteoporosis.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China. lung1212@hku.hk
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Cheung
authors.forename: Kam-Shing
authors.initials: KS
authors.lastname: Lau
authors.forename: Pak-Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Kathryn C B
authors.initials: KC
authors.lastname: Tan
authors.forename: Annie W C
authors.initials: AW
authors.lastname: Kung
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D002681:China; D016207:Cytokines; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D013131:Spine / Q000000981:diagnostic imaging
chemical_list: D016207:Cytokines; C495107:GREM2 protein, human; D036341:Intercellular Signaling Peptides and Proteins