Rs3729547

rs3729547, is a SNP that was recently shown to be mildly associated with dilated cardiomyopathy (DCM) in the Han Chinese population and hypertrophic cardiomyopathy in the Indian population. . This SNP is located within the coding sequence of the TNNT2 gene, which encodes a component of the troponin complex critical for proper sarcomeric contractility in cardiomyocytes, the cell type driving contraction in the heart.

A number of earlier studies have shown that mutations in TNNT2 can lead to dilated cardiomyopathy. characterized by a thinning of the ventricular wall, or conversely, hypertrophic cardiomyopathy (HCM), characterized by a thickening of the ventricular wall. Both conditions lead to an overall weakening of the heart muscle and can lead to heart failure or sudden cardiac death. The molecular mechanisms whereby mutations in the same gene (TNNT2) can lead to two diseases (DCM and HCM) with such contrasting phenotypes are still not well-understood.

In a study by Li et al, rs3729547 (C to T) and another tagging SNP also in TNNT2, rs3729843 (G to A), were shown to be associated with DCM in a cohort of Han Chinese individuals (X2= 6.63, P = 0.036; X2 = 9.787, P = 0.008, respectively) The risk allele for rs3729547 is T and the risk allele for rs3729843 is A. rs3729547 is a synonymous (isoleucine) variant whereas rs3729843 is a noncoding SNP. In this study, the authors investigated the association between 10 tagging SNPs (these two included) and DCM using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF-MS). However, the patients from this study were all members of the Han Chinese population, and therefore, these SNPs must be studied in the context of another ethnic group to validate strong associations between these SNPs and DCM. Additionally, this study was limited by its sample size, as only 97 DCM patients and 189 healthy unrelated controls partook in this study.

In a second study published by Rani et al, the TNNT2 gene was sequenced in 162 patients with hypertrophic cardiomyopathy (HCM) and in 179 healthy controls. HCM phenotype ranged from moderate to severe, but a limited number of corrective operations were performed in these HCM patients. In contrast to the Li et al paper, this study was conducted exclusively in patients from India. Fifteen associated variants were uncovered, including rs3729547 (C to T) and rs3729843 (G to A), which were found to be in high linkage disequilibrium in the HCM patients. They also identified a 5bp deletion polymorphism in this Indian population that was previously shown to be associated with HCM patients of French, Spanish, and Japanese origin.