Meta-analysis of methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and risk of orofacial cleft

Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of orofacial cleft (OFC) and several studies were published with conflicting results. A meta-analysis of the previous studies of allelic association between OFC with A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene was carried out. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR A1298C polymorphism and OFC risk. A total of 11 studies including 1628 cases and 2676 controls were involved in this meta-analysis. No statistical relationship was found with any genetic model (C vs. A (Additive): OR = 1.14, 95%CI = 0.76-1.65, P = 0.47; CC vs. AA (homozygote): OR = 0.90, 95%CI = 0.72-1.15, P = 0.0.41; AC vs. AA (co-dominant): OR = 0.97, 95%CI = 0.85-1.11, P = 0.0.63; CC+AC vs. AA (Dominant): OR = 0.96, 95%CI = 0.84-1.1 , P = 0.51; CC vs. AC+AA (Recessive): OR = 0.93, 95%CI = 0.74-1.16, P = 0.52). The present meta-analysis supports that the common A1298C polymorphism of MTHFR gene is not risk factor for OFC.   Key words: Orofacial cleft, cleft lip, cleft palate, methylenetetrahydrofolate reductase (MTHFR), A1298C, folic acid.