Studies of the Candidate Genes TGFB2,MSX1,TGFA,and TGFB3 in the Etiology of Cleft Lip and Palate in the Philippines

Population-based candidate-gene studies can be an effective strategy for identifying genes involved in the etiology of disorders where family-based linkage studies are compromised by lack of access to affected members, low penetrance, and/or genetic heterogeneity. We evaluated association data for four candidate genes using a population from the Philippines that Is genetically separate from previously studied Caucasian populations. Case ascertainment was made possible by collaboration with Operation Smile, a volunteer medical organization, which facilitated Identification of a large number of cases for study. A new allelic variant of transforming growth factor-beta3 was identified to use in these studies. After exclusion of syndromic cases of cleft lip and palate, no evidence for association with previously reported allelic variants of transforming growth factor-beta2 (TGFB2), homeobox 7 (MSX1), or transforming growth factor-alpha (TGFA), or with the new TGFB3 variant was detected. Previous association studies using Caucasian populations of nonsyndromic cleft lip and/or palate (CUP) and cleft palate only (CPO) have strongly suggested a role for TGFA in the susceptibility of clefting in humans. Exclusion of significant association in a non-Caucasian population for TGFA suggests that TGFA plays less of a role than it does in Caucasians. This may be due to multiple or different genetic and/or environmental factors contributing to the etiology of this most common craniofacial anomaly in the Philippine population.