title: IRF6 Is a Marker of Severity in Nonsyndromic Cleft Lip/Palate.
abstract: Nonsyndromic cleft lip with or without palate (CL/P) is thought to be caused by the interplay of genetic and environmental factors, and this has thus hindered the process of identifying genetic causative factors. Numerous studies in the past decade have implicated IRF6 in CL/P, but this has not often been replicated in other populations. In specific, the only etiologic single-nucleotide polymorphism (SNP) identified in the IRF6 locus (rs642961) has recently been shown not to be associated with CL/P in diverse populations. We therefore used a genewide tagging SNP (tagSNP) haplotyping approach (including rs642961 as a tagSNP) to detect all potential risk-conferring haplotypes and combined this with detailed subphenotyping of CL/P cases (N = 150) according to severity. We observed a significant overrepresentation of a tagSNP haplotype carrying the rs642961 risk allele in the most severe subphenotype of CL/P (complete bilateral CL/P; P = 0.008, odds ratio = 4.97, 95% confidence interval = 1.33 to 18.46). It was recently shown that >80% of IRF6 mutations in syndromic CL/P occur on the same haplotype background. We therefore suggest that IRF6 is a marker of CL/P severity.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Kerameddin
authors.affiliation: Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Namipashaki
authors.affiliation: Faculty of New Sciences and Technology, University of Tehran, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Ebrahimi
authors.affiliation: Faculty of New Sciences and Technology, University of Tehran, Tehran, Iran n.ansaripour@ut.ac.ir.
authors.forename: N
authors.initials: N
authors.lastname: Ansari-Pour
mesh_terms: D000225:Adenine; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000145:classification / Q000235:genetics*; D002972:Cleft Palate / Q000145:classification / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D013941:Thymine
chemical_list: D014408:Biomarkers, Tumor; C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D006147:Guanine; D000225:Adenine; D013941:Thymine
keywords: congenital; genetic heterogeneity; haplotypes; medical genetics; odds ratio; single nucleotide polymorphism