Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

ObjectiveNonsyndromic cleft lip with or without cleft palate(NSCL/P) is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6(IRF6) gene and transforming growth factor-a(TGFA) gene seem to be crucial in the predisposition of NSCL/P. Here we evaluated some single nucleotide polymorphisms(SNPs) loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P.MethodsFifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk(HRR) and Transmission Disequilibrium Test(TDT) were performed.ResultsThe sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus of IRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis.ConclusionOur study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.