ROLE OF TRANSCRIPTION FACTOR GENE POLYMORPHISMS IN THE PATHOGENESIS OF NON SYNDROMIC CLEFT LIP WITH OR WITH OUT CLEFT PALATE A CASE CONTROL STUDY

Abstract

newlineThis thesis describes the association of the transcription factors gene polymorphisms with non syndromic cleft lip with or without cleft palate NSCLP The thesis is based on a case control study on south Indian NSCLP The 173 subjects with NSCLP included as cases and 176 age and sex matched healthy subjects without family history of clefting were recruited as controls Overall 20 important single nucleotide polymorphisms in seven IRF6 TFAP2A MAFB ABCA4 SATB2 TBX22 and MSX1 candidate genes were selected The genotyping was done by both PCR RFLP method and KASPar SNP genotype method Genotyping of 20 SNPs from seven genes revealed that the Hardy Weinberg expectations were fulfilled in controls for all SNPs except TBX22 rs7055763 SNP in females IRF6 rs2235371 and rs2235375 significantly associated with increased risk of NSCLP MAFB rs13041247 and rs11696257 were surrogates and significantly associated with risk of CLP TFAP2A and ABCA4 gene polymorphisms were not associated with NSCLP TFAP2A and ABCA4 gene polymorphisms were not associated with NSCLP SATB2 variants were not associated with NSCLP MSX1 rs11726039 variant showed reduced risk of NSCLP No LD was found between SNPs of IRF6 TFAP2A ABCA4 MSX1 and SATB2 genes The MAFB and TBX22 SNPs were in strong LD The genotype genotype interaction analysis had also shown significant synergetic interaction between SATB2 rs1992950 and IRF6 rs2235375 SNPs Ultimately this work supports the hypothesis for the involvement of transcription factors gene SNPs in the susceptibility of NSCLP