Association of single-nucleotide polymorphisms in the IRF6 gene with non-syndromic cleft lip with or without cleft palate in the Xinjiang Uyghur population.

Our main aim was to investigate the association between the interferon regulatory factor (IRF6) gene and non-syndromic cleft lip and palate (nsCLP) in the Xinjiang Uyghur population. Twelve single nucleotide polymorphisms (SNP) were screened in a group of 100 patients with nsCLP and in a control group of 60 unaffected subjects by next generation sequencing using a MiSeq Benchtop Sequencer (Illumina). Our case-control association analysis showed that the SNP marker rs7545538 differed significantly in genotype (codominant model; CC compared with CG compared with GG; p=0.038) and allele frequencies (odds ratio (OR)=1.89, 95% CI 1.18-3.03, p=0.007) between patients with nsCLP and controls. Analysis of the recessive model of inheritance showed that distribution of the recessive model of rs7545538 (GG compared with CC+GC) was significantly higher in patients with nsCLP than in controls (OR=2.5, 95% CI 1.13-5.37, p=0.021) and had a borderline association with an increased risk of nsCLP (OR=2.5, 95% CI 1.13-5.37, p=0.021). Markers rs2235377 and rs2235371 also differed significantly in dominant and over-dominant models of inheritance (p=0.037) while increased G allele frequency was seen in SNP rs2235373 (p=0.03). A haplotype analysis showed four common haplotypes in Block 1: CCGGT>CCGAT>CACAT>TAGAC (in frequency). The 5-marker combination haplotype CCGAT was significantly more common in patients with nsCLP than in controls (p=0.032). In Block 2, the overall distribution of the haplotypes TAC and TAG predicted by the three SNP differed significantly between the patients with nsCLP and control subjects (p=0.009 and 0.003, respectively). Our results showed that genetic polymorphism of the IRF6 gene is associated with increased risk of nsCLP in a Xinjiang Uyghur population.