title: Further evidence of association of the ABCA4 gene with cleft lip/palate.
abstract: Non-syndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. Numerous genes and environmental factors, and their interactions, are thought to play a role in the susceptibility to CL/P. A recent genome-wide association study with several populations revealed markers in/near transcription factor vmaf musculoaponeurtoic fibrosarcoma oncogene homolog B (MAFB) and ATP-binding cassette sub-family A member 4 (ABCA4) genes as new susceptibility loci for CL/P. We hypothesized that these genes could also contribute to CL/P in a Brazilian population, and hence we evaluated if the associated single-nucleotide polymorphisms (SNPs) in MAFB (rs13041247 and rs11696257) and ABCA4 (rs560426 and rs481931) were associated with CL/P in our case-control data set. We genotyped 812 Caucasian individuals (400 cases and 412 controls) from Brazil. Allele frequencies were compared for cases and controls as well as for cleft subgroups and controls. ABCA4 rs540426 showed strong associations with CL/P, unilateral and right CL/P, and bilateral CL/P, whereas the SNP rs481931 showed borderline associations with CL/P and bilateral CL/P . No association was found for MAFB. Our results support a potential role for ABCA4 in the etiology of CL/P in individuals from Brazil.
authors.affiliation: Department of Cell and Molecular Biology, Fluminense Federal University, Niteroi, RJ, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Fontoura
authors.forename: Renato M
authors.initials: RM
authors.lastname: Silva
authors.forename: Jose M
authors.initials: JM
authors.lastname: Granjeiro
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051258:MafB Transcription Factor / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D051258:MafB Transcription Factor