Genetic Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Osteonecrosis of the Femoral Head

BACKGROUND Methylenetetrahydrofolate reductase (MTHFR) SNP rs1801133 has been frequently investigated in recent years. Relevant candidate gene association studies with this SNP and osteonecrosis of the femoral head (ONFH) reported conflicting results. Meta-analysis provides a method to combine these data and to determine the association in a larger sample size. METHOD We conducted a systematic search to identify possible studies. Four pooled ORs (odds ratios, T versus C, TT versus CC, TT/CT versus CC, and TT versus CT/CC), along with 95% confidence interval (CI), were calculated to evaluate the association between SNP rs1801133 and ONFH susceptibility. Both fixed effects model and random effects model were used. FINDINGS We eventually included twelve studies in this analysis, with results showing no overall association between ONFH susceptibility and SNP rs1801133 (T versus C: OR=1.15, 95% CI=0.97-1.38; TT versus CC: OR=1.15, 95% CI=0.91-1.46; TT/CT versus CC: OR=1.09, 95% CI=0.95-1.25; and TT versus CT/CC OR=1.16, 95% CI=0.93-1.45). When stratified based on ethnicity, the results were still not significant. CONCLUSION Our findings are generally supportive of no association between MTHFR SNP rs1801133 and the etiology of ONFH.