Association Of Single Nucleotide Polymorphisms In IRF6 And TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate In Chinese Patients

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is acommon birth defect with unclear etiology. Both genetic andenvironmental factors may contribute to NSCL/P. Many genes have beenidentified as candidate genes associated with this disease. Interferonregulatory factor 6 (IRF6) gene and transforming growth factor-α(TGFA)gene seem to be crucial to predisposition of NSCL/P. Here we evaluatedsome single nucleotide polymorphisms (SNPs) loci of TGFA and IRF6genes in Chinese nuclear families consisting of fathers, mothers andaffected offspring with NSCL/P by applying microarray technology.Some PCR products were randomly chosen and sequenced to check theresult from microarraies. The distribution of gene type and allelefrequency between patient group and parents group were compared. ThenHaplotype Relative Risk (HRR) and Transmission Disequilibrium Test(TDT) were performed. The sequences of randomly selected PCRproducts were all consistent with the results of microarraies. All loci werein Hardy-Weinberg equilibrium. There were no significant difference in genotypes and alleles distribution between patients and their parents. TheV274I of IRF6 was associated with NSCL/P while another SNP locus ofIRF6 was not in neither HRR nor TDT analysis. Strong evidences oflinkage disequilibrium were found between the 2 SNP loci of TGFA anddisease with the HRR analysis, but not with the TDT analysis. Thus ourstudies confirm the contribution of IRF6 in the etiology of NSCL/P inpopulations of Asian ancestry. The association of TGFA with NSCL/Pneeds further research. It's efficient to use the microarray to detect SNPscite. This study confirmed that genetic factors contributed to the etiologyof NSCL/P. The results might answer the question from part of thepatients that why they were affected by this disease. It's more importantto use the results to find out high-risk groups in advantage so that theincidence of NSCL/P will be reduced.