Contribution of Transforming Growth Factor α Polymorphisms to Nonsyndromic Orofacial Clefts: A HuGE Review and Meta-Analysis

We performed a meta-analysis of the association of transforming growth factor gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP). In total, data from 29 studies were pooled for the following 3 polymorphisms: TGFA/TaqI, TGFA/BamHI, and TGFA/RasI in the TGFA gene. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A significantly increased CL/P or CP risk was observed in persons carrying a C2 allele at the TaqI polymorphism (odds ratio (OR) 1.70, 95 confidence interval (CI): 1.41, 2.05) compared with those with a C1 allele (OR 1.57, 95 CI: 1.23, 2.01). For the TGFA/BamHI polymorphism, carriers of the minor A1 allele had an estimated relative decrease in CL/P risk (OR 0.44, 95 CI: 0.30, 0.64). These associations remained significant when only high-quality studies were included. However, no significant association was observed between the TGFA/RasI variant and CL/P risk. In summary, this meta-analysis provided a robust estimate of the positive association of the TGFA/TaqI polymorphism with both CL/P and CP and suggests that persons with an A1 allele may have a markedly decreased risk of CL/P.