title: Studies of the candidate genes TGFB2, MSX1, TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines.
abstract: 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-beta 3 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-beta 2 (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 (CL/P) 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 cranio-facial anomaly in the Philippine population.
authors.affiliation: Department of Orthodontics, University of Iowa, Iowa City 52242-1083, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Lidral
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
authors.forename: K H
authors.initials: KH
authors.lastname: Buetow
authors.forename: A M
authors.initials: AM
authors.lastname: Basart
authors.forename: H
authors.initials: H
authors.lastname: Schearer
authors.forename: R
authors.initials: R
authors.lastname: Shiang
authors.forename: A
authors.initials: A
authors.lastname: Naval
authors.forename: E
authors.initials: E
authors.lastname: Layda
authors.forename: K
authors.initials: K
authors.lastname: Magee
authors.forename: W
authors.initials: W
authors.lastname: Magee
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004777:Environment; D005260:Female; D005801:Genes, Homeobox / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051957:MSX1 Transcription Factor; D008297:Male; D008969:Molecular Sequence Data; D010679:Philippines; D011159:Population Surveillance; D013577:Syndrome; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D014157:Transcription Factors; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta