A study on transcription factors tbx1nkx25 and variants of folate metabolism genes in conotruncal heart defects

Abstract

To identify an association between a homogenous group of congenital heart malformations with mutations or variations in selected candidate genes 100 cases with conotruncal heart defects CTHD and 100 age matched controls were recruited. Since cytogenetic screening of the cases diagnosed with CTHD was the primary step for inclusion in mutation analysis chromosomal analysis and FISH for the 22q11microdeletion was performed while 3 of the cases showed chromosomal abnormalities 1showed the 22q11 micro deletion TBX1 a transcription factor of the T-box family is known to have an important role in the regulation of cardiac developmental processes and was screened for mutations by PCR Sanger sequencing Neither the cases nor the control subjects showed any mutations or sequence variants NKX25 is expressed during early cardiac morphogenesis and functions as a pivotal regulatory protein. While a somatic mutational frequency of 6 was detected in the cardiac tissue DNA a mutational frequency of 11 was observed in the lymphocytic DNA A marginal but significant fold change in gene expression in the tissue samples relative to the blood samples was also seen SNP in genes that code for key enzymes in the folate pathway may alter metabolic activity and influence the risk for CTHD Logistic regression analyses revealed that for the rs1801131 genotypes subjects carrying the CC variant homozygote had a significant association with the risk of CTHD For the mothers who did not have periconceptional vitamins there was a significant difference between cases and controls for the CC genotype of MTHFR rs1801131 A greater C implying that the absence of sufficient folic acid could increase the risk for CTHD risk in infants with the variant genotype newline