title: Association of MTHFR C667T polymorphism with bone mineral density and fracture risk: an updated meta-analysis.
abstract: This meta-analysis investigated the association of C677T polymorphism in MTHFR gene with bone mineral density (BMD) and fracture risk. The results suggested that C677T polymorphism was marginally associated with fracture risk. In addition, this polymorphism was modestly associated with BMD of lumbar spine, femoral neck, total hip, and total body, respectively.
  
  
  BACKGROUND
  The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the regulation of BMD and, thus, may serve as a potential risk factor for the development of fracture. However, results have been inconsistent. In this study, a meta-analysis was performed to clarify the association of C677T polymorphism in MTHFR gene with BMD and fracture risk.
  
  
  METHODS
  Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) or weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model.
  
  
  RESULTS
  Twenty studies (3,525 cases and 17,909 controls) were included in this meta-analysis. The TT genotype of C677T polymorphism was marginally associated with an increased risk of fracture under recessive model (TT vs. TC + CC: OR = 1.23, 95% CI 1.04-1.47). Using this model, similar results were found among East Asians (OR = 1.40, 95% CI 1.07-1.83), female subpopulation (1.27, 95% CI 1.04-1.55), cohort studies (OR = 1.24, 95% CI 1.08-1.44), and subjects younger than aged 60 years (OR = 1.51, 95% CI 1.10-2.07). In addition, under homogeneous co-dominant model, there was a modest association of C677T polymorphism with BMD of lumbar spine (WMD = -0.017 g/cm(2); 95%CI, -0.030-(-0.005) g/cm(2)), femoral neck (WMD = -0.010 g/cm(2); 95% CI -0.017-(-0.003) g/cm(2)), total hip (WMD = -0.013 g/cm(2), 95% CI -0.022-(-0.004) g/cm(2)), and total body (WMD = -0.020 g/cm(2); 95% CI -0.027-(-0.013) g/cm(2)), respectively.
  
  
  CONCLUSIONS
  This meta-analysis suggested that C677T polymorphism was marginally associated with fracture risk. In addition, this polymorphism was modestly associated with BMD of lumbar spine, femoral neck, total hip, and total body, respectively.
authors.affiliation: Department of Orthopedics, Taizhou Municipal Hospital, Taizhou, 318000, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Liu
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005272:Femur Neck / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006621:Hip Joint / Q000502:physiology; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics; D058866:Osteoporotic Fractures / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017594:Publication Bias
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)