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.

Association between IRF6, TP63, GREM1 Gene Polymorphisms and Non-Syndromic Orofacial Cleft Phenotypes in Vietnamese Population: A Case–Control and Family-Based Study

“…The TDT results in the triad analysis are worth mentioning, with the significant over-transmission of the G allele with NSCL/P (p = 0.0020; OR = 1.34), suggesting that offspring who inherited the G allele at rs2235375 had a 1.34-fold increased risk of NSCL/P compared to the C allele holders. The same results were seen in Mexican [41], European-American [37], Taiwanese, Singaporean, Korean and Western Chinese case-parent triads in a genome-wide TDT anal-ysis [35]. However, we did not detect significant distortion in the allele transmission of rs2235375 from parents to affected progeny in any cleft phenotypes using the POO analysis.…”

Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with or without cleft palate: Systematic review and meta‐analysis

“…Exploring this would require individual patient data where data for folate and other covariables are also available. Third, we could not identify which polymorphism is the disease gene among those three polymorphisms in IRF6 gene because evidences showed linkage disequilibrium between rs2235371 and rs2013162 in Mexican (Ibarra-Arce et al, 2015) and Chinese (Mijiti et al, 2015) population (r 2 5 0.39 and 0.25, respectively) but not for rs642961 (Pan et al, 2010) (r 2 5 0.07). To determine this required raw data for performing a haplotype analysis.…”

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population

“…This polymorphism showed the positive association between this variant and NSCL/P in several populations such as Italian, 7 European-Americans, 25 Norwegian, 39 Chilean, 28 Chinese 40 and Brazilian. 41 …”