Strong Evidence of Linkage Disequilibrium between Polymorphisms at the IRF6 Locus and Nonsyndromic Cleft Lip With or Without Cleft Palate, in an Italian Population

• Published in: American journal of human genetics Vol. 76; no. 1; pp. 180 - 183
• Main Authors: Scapoli, Luca, Palmieri, Annalisa, Martinelli, Marcella, Pezzetti, Furio, Carinci, Paolo, Tognon, Mauro, Carinci, Francesco
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.01.2005; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Biological and medical sciences; Cleft Lip - genetics; Cleft Palate - genetics; DNA-Binding Proteins - genetics; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Gene loci; General aspects. Genetic counseling; Genetic linkage; Genetic markers; Genetic Predisposition to Disease; Genetics; Humans; Interferon Regulatory Factor-1; Interferon-gamma - genetics; Italy; Linkage Disequilibrium; Male; Medical genetics; Medical sciences; Mouth; Non tumoral diseases; Otorhinolaryngology. Stomatology; Phosphoproteins - genetics; Polymorphism; Polymorphism, Genetic; Transcription Factors - genetics; Italy; Human; Italian; Cleft lip; Malformation; Stomatology; Genetics; Population; Oral cavity disease; Linkage equilibrium; Locus; Congenital disease; Polymorphism
• DOI: 10.1086/427344
• ISSN: 0002-9297

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.