INFLUENCE OF TGF-1509 C / T AND 869 T / C POLYMORPHISMS ON CHANNEL CONDUCTIVITY IN LONG QT SYNDROME

Long QT syndrome (LQTS) manifests itself with syncopal episodes ending in sudden cardiac death and abnormalities in the electrophysiology of the heart. The main cause of LQTS is the mutated ion channels encoded by faulty genes. Transforming growth factor-beta 1 is a cytokine involved in the development of cardiomyocytes. Incomplete penetrance and variable expressivity are phenomena commonly observed in LQTS; hence; the role of modifiers such as TGF-1 can be expected. A total of 219 unrelated control samples and 49 cases with 71 family members were enrolled for the study. Five ml of venous blood was collected from all the individuals and genomic DNA was isolated by standard protocol. Genotyping was performed for the two TGF-1 polymorphisms (-509C/T and 869T/C) by Allele specific PCR followed by calculation of relative risk estimates and in silico prediction of premRNA secondary structures. Relative risk estimates showed a significant association between the “TC” genotype of the 869T/C polymorphism and LQTS. This was further corroborated by the “C” allele‟s pre-mRNA secondary structure of the 869T/C polymorphism. A significant association between the “TC” genotype and the “C” allele of the 869T/C polymorphism and LQTS was observed. The heterozygote disadvantage exhibited by “TC” could lead to expression of a haplo-insufficient protein product ending in improper folded ion channels or faulty anchoring of the ion channels.