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Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigentic process of DNA methylation. It has been reported that abnormal DNA methylation contributes to the pathogenesis of congenital anomalies. There were many published case control studies assessing the associations of MTHFR C677T polymorphism with risks of nosyndromic cleft lip with and without palate (nsCL/P), but with inconsistent results. To derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified by search of databases including PubMed, Science Direct, Google Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies with 3724 nsCL/P cases and 5275 controls were included in the present meta-analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association. Subgroup analysis based on ethnicity was also performed. All statistical analyses were done by MIX program. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased nsCL/P risk in overall population using four genetic models except homozygote model (for T vs. C: OR = 1.24, 95% CI = 1.1-1.4; for TT + CT vs. CC: OR = 1.29, 95% CI = 1.04-1.59; for CT vs. CC: OR = 1.26, 95% CI = 0.98-1.63; for TT vs. CC: OR = 1.02, 95% CI = 0.74-1.4; for TT vs. CT + CC: OR = 1.36, 95% CI = 1.05-1.74). In conclusion, results of present meta-analysis suggested that MTHFR C677T polymorphism is significantly associated with nonsyndromic orofacial cleft.

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P)