title: Association of single-nucleotide polymorphisms in the IRF6 gene with non-syndromic cleft lip with or without cleft palate in the Xinjiang Uyghur population.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China; Stomatological Research Institute of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830054, People's Republic of China.
authors.forename: Ainiwaer
authors.initials: A
authors.lastname: Mijiti
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China; Stomatological Research Institute of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830054, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ling
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China; Stomatological Research Institute of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830054, People's Republic of China.
authors.lastname: Guli
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, People's Republic of China; Stomatological Research Institute of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830054, People's Republic of China. Electronic address: adili928@hotmail.com.
authors.forename: Adili
authors.initials: A
authors.lastname: Moming
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000225:Adenine; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003596:Cytosine; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006147:Guanine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007438:Introns / Q000235:genetics; D007532:Isoleucine / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012694:Serine / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D007532:Isoleucine; D012694:Serine; D006147:Guanine; D003596:Cytosine; D014633:Valine; D000225:Adenine
keywords: Case–control study; IRF6 gene; Linkage disequilibrium; Orofacial clefts