Association of single nucleotide polymorphisms in the IRF6 gene with nonsyndromic cleft lip with or without cleft palate in Kinh Vietnamese patients

Background The interferon regulatory factor 6 (IRF6) gene, which causes Van der Woude syndrome, is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P). Single nucleotide polymorphisms (SNPs) in the IRF6 gene were identified as susceptibility indicators of this defect in several populations. To further evaluate its role in this birth defect, we conducted this study with the aim of identifying allele frequencies, genotype frequencies, and associations of 5 SNPs (rs2235373, rs2235371, rs2235375, rs2013162, and rs2236907) in the IRF6 gene with NSCL/P in Kinh Vietnamese patients. Methods A total of 132 patients with NSCL/P and 132 healthy individuals were included in our study group. Direct sequencing was performed to genotype the tag SNPs. Genetic models were used to compare genotype and allele frequencies between the case and control groups. Results In the recessive model, the genotypes C/C of rs2236907, C/C of rs2013162, G/G of rs2235375, and A/A of rs2235373 were associated with an increased risk of NSCL/P, whereas there was no clear association between rs2235371 and the malformation in any genetic model. When subgroup analysis was performed, we observed a similar risk trend in the cleft lip and palate, cleft palate only and cleft lip only phenotypes. In haplotype analysis, haplotype models of 5 tag SNPs were associated with increased risks of this defect in all phenotypic models (ORGCGCC/CCAA = 23.64, 95% CI 12.28-45.49, p < 0.0001). Conclusions These findings point to a considerable contribution of rs2236907, rs2013162, rs2235373, and rs2235375 to the NSCL/P defect in Kinh Vietnamese individuals.

Automated summary

This study found an association between five SNPs in the IRF6 gene and the risk of NSCL/P in the Vietnamese population. The genotypes of rs2236907, rs2013162, rs2235373, and rs2235375 were found to be associated with an increased risk of NSCL/P.