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 polymor-phismwith bothCL/PandCPand suggests that personswith anA1 allelemay have amarkedly decreased riskof CL/P. cleft lip with or without cleft palate; cleft palate; epidemiology; genetic association studies; genetics; meta-analysis; polymorphism; transforming growth factor α Abbreviations: BMP4, bone morphogenetic protein 4 gene; CI, confidence interval; CL/P, cleft lip with or without cleft palate; CP, cleft palate; HWE, Hardy-Weinberg equilibrium; IRF6, interferon regulatory factor 6 gene; MTHFR, methylenetetrahydrofolat