title: IRF6 polymorphisms in Mexican patients with non-syndromic cleft lip.
abstract: Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects; it is a multifactorial disease affecting > 1/1,000 live births in Europe, and its etiology is largely unknown, although it is very likely genetic and environmental factors contribute to this malformation. Orofacial development is a complex process involving many genes and signaling pathways. Mutations in the gene for the interferon regulatory factor 6 (IRF6) cause a hereditary dominant malformation syndrome including CL/P, and polymorphisms are associated with non-syndromic CL/P (MIM 119530). Five SNPs at the locus with high heterozygosity in Caucasian populations were chosen for the present research due to their very strong association with CL/P. A case-parent trio study was performed using 292 samples from Mexico. Association with the rs1319435-C/C genotype (P = 0.02) was found in patients (73) as compared to pseudocontrols (219), while the genotype rs1319435-T/C was related with protection (P = 0.041) in the triad design. Significant over-transmission of the G allele for marker rs2235375 (P = 0.049) was found. Only the TACGT haplotype was diminished in the affected child, either in single (P = 0.0208) or double (P = 0.0208) dose. The pairwise analysis showed rs2235543 and rs2235371 were in strong linkage disequilibrium. These results point to a substantial contribution of IRF6 in the etiology of non-syndromic CL/P in a sample of the Mexican population.
authors: División de Genética, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Aurora
authors: A
authors: Ibarra-Arce
authors: División de Genética, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Martín
authors: M
authors: García-Álvarez
authors: Departamento de Biología Molecular e Histocompatibilidad, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Daniel
authors: D
authors: Cortés-González
authors: División de Genética, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Gabriela
authors: G
authors: Ortiz de Zarate-Alarcón
authors: División de Genética, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Laura
authors: L
authors: Flores-Peña
authors: División de Genética, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Sandra
authors: S
authors: Sánchez-Camacho
authors: Instituto Nacional de Rehabilitación, Mexico DF, Mexico.
authors: Silvia
authors: S
authors: Arenas-Díaz
authors: Departamento de Biología Molecular e Histocompatibilidad, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Mirza
authors: M
authors: Romero-Valdovinos
authors: Departamento de Biología Molecular e Histocompatibilidad, Hospital General Doctor Manuel Gea González, Mexico DF, Mexico.
authors: Angélica
authors: A
authors: Olivo-Díaz
keywords: Birth defects; Cleft lip; Cleft palate; Congenital abnormalities; Craniofacial development; IRF6