title: Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and nonsyndromic cleft lip with or without cleft palate, in an Italian population.
abstract: Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects, but its etiology is largely unknown. It is very likely that both genetic and environmental factors contribute to this malformation. Mutations in the gene for interferon regulatory factor 6 (IRF6) have been shown to be the cause of Van der Woude syndrome, a dominant disorder that has CL/P as a common feature. Recently, it has been reported that genetic polymorphisms at the IRF6 locus are associated with nonsyndromic CL/P, with stronger association in Asian and South American populations. We investigated four markers spanning the IRF6 locus, using the transmission/disequilibrium test. A sample of 219 Italian triads of patients and their parents were enrolled in the study. Strong evidence of linkage disequilibrium was found between markers and disease in both single-allele (P=.002 at marker rs2235375) and haplotype (P=.0005) analyses. These findings confirm the contribution of IRF6 in the etiology of nonsyndromic CL/P and strongly support its involvement in populations of European ancestry.
authors.affiliation: Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Via Fossato di Mortara 64/B, 44100 Ferrara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scapoli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Palmieri
authors.forename: Marcella
authors.initials: M
authors.lastname: Martinelli
authors.forename: Furio
authors.initials: F
authors.lastname: Pezzetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Carinci
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
mesh_terms: D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000235:genetics; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D014157:Transcription Factors; D007371:Interferon-gamma