Human Genome Epidemiology (HuGE) Review Contribution of Transforming Growth Factor α Polymorphisms to Nonsyndromic Orofacial Clefts: A HuGE Review and Meta-Analysis

We performed ameta-analysis of the association of transforming growth factor α 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 increasedCL/PorCP riskwas observed in persons carrying aC2 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 inCL/P risk (OR= 0.44, 95%CI: 0.30, 0.64). These associations remained significantwhenonly 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 polymorphismwith bothCL/PandCPand suggests that personswith anA1 allelemay have amarkedly decreased riskof CL/P.