Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate in Brazilian patients: results of a large case-control study.

Objective: Transforming growth factor-alpha (TGFA) was the first gene suggested to be associated with nonsyndromic cleft lip, cleft palate, or both (CL/ P). There are, however, still controversies of the effect of TGFA on the predisposition of this malformation. To contribute to a better understanding of the role of this gene in the occurrence of CL/P we undertook a case-control study including patients and controls ascertained in different regions of the country.

Design: We examined the C2/TaqI variant of the TGFA gene in 536 patients with nonsyndromic CL/P and 412 controls. The TGFA genotype frequencies in patients were compared with controls using chi-square or Fisher exact test. DNA, obtained from peripheral blood or buccal swabs, was genotyped for the TaqI polymorphism of TGFA.

Setting: The probands and corresponding controls were ascertained in different centers of Brazil, partly representing the ethnic admixture of our population.

Results: The TGFA genotype distribution was very similar in patients with CL/P ascertained in the three different regions of Brazil. However, a discrete difference was observed between controls of Säo Paulo and Ceará (chi-square = 3.605; p = 0.058), with a lower value of the C2/Taq allele frequency in controls of CE (0.04). These data reinforce that this polymorphic system is heterogenous among different ethnic groups. In addition, no evidence was found for an association of TGFA with CL/P in this case-control study.

Conclusion: These data further suggest that TGFA is not a relevant modifier locus for the occurrence of CL/P.