A Common 5bp (CTTCT) Deletion Polymorphism in TNNT2 is Significantly Associated with Hypertrophic Cardiomyopathy

Troponin T is a component of the Troponin complex, which plays a major role in the regulation of myocardial contraction in response to changes in the intracellular Ca2+ion concentration. Deletion of 5bp (CTTCT) in the polypyrimidine tract of intron 3 of the cardiac Troponin T gene (TNNT2) results in cTnT2 and cTnT4 isoforms by skipping of exon 4, which was reported to be associated with hypertrophic cardiomyopathy (HCM). In the present study, we screened a common 5bp deletion polymorphism in TNNT2 gene using direct sequencing in 178 cardiomyopathy patients with significant LV hypertrophy from North India against 197 ethnically matched and clinically well-characterized healthy controls. Our study revealed a high frequency of del/del genotype in patients with HCM vs controls (p=0.000007). The deletion and insertion allele frequencies in patients and controls were (75% & 25%) and (56% & 44%), respectively. Further, analysis of 2056 caste and tribe groups belonging to highly diverse endogamous people inhabited in different states of India have revealed higher deletion allele frequency in both South and North Indian states compare to control group whereas the North-eastern states showed a slightly higher frequency of insertion allele. In conclusion, the deletion allele frequency in the HCM patient group is found to be significantly higher than the control group (p=<.0001). Therefore, the deletion allele frequency is not only associated with LV hypertrophy in Japanese, French, and South Indian HCM patients but also in North Indian HCM patients.