Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations

Abstract

Purpose:The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations. Methods: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models. Results: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over-and undertransmission among Taiwanese cases (P ϭ 9 ϫ 10 Ϫ6 and P ϭ 5 ϫ 10 Ϫ6 , respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P Ͻ

Interferon Regulatory Factor 6 (IRF6) and Gene – Environment Interactions in Non-Syndromic Orofacial Cleft Cases in Saudi Arabia-A Case Control Study

“…This finding is supported by other studies that investigated the relationship between NSOFC and IRF6 and included CP cases in their sample [6,14,21].…”

“…In addition, PLINK analysis showed a protective effect and an association between the rare A allele and CL(P) (P=0.018 and OR: 0.644 for CL(P)). A similar finding was reported by Scapoli et al [14], who detected an over-transmission of the common allele for rs2013162 (P=0.004) and all haplotypes carrying these common alleles among 219 Italian CL(P) trios. This is also similar to the finding reported by Park et al [15] and Blanton et al [16].…”

Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts

“…IRF6 has also been consistently associated with CL/P in a number of populations. [17][18][19][20][21][22] In the same way, MSX1 has been associated with CL/P in several independent studies. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] We hypothesize that increasing the sophistication of the clinical description would allow reducing misclassification and improving ones ability to see associations that may have been otherwise masked by a larger more heterogeneous classification approach.…”

Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic cleft lip with or without cleft palate risk in the Slovak population

“…A variety of genetic approaches have been used to identify genes and pathways underlying nsCL/P. Before 2009, only one gene (interferon regulatory factor 6, IRF6) had been identified with a sufficient degree of consistency across studies, thus being considered a true nsCL/P-associated gene [7][8][9] . Association of nsCL/P with single nucleotide polymorphism (SNP) rs642961 in the IRF6 gene located at chromosomal region 1q32 was confirmed in candidate gene and genome-wide association studies (GWAS) of European-derived populations [10][11] .…”