miRNA regulation during cardiac development and remodeling in cardiomyopathy.

miRNAs have been found to play a major role in cardiomyopathy, a heart muscle disorder characterized by cardiac dysfunction. Several miRNAs including those involved in heart development are found to be dysregulated in cardiomyopathy. These miRNAs act either directly or indirectly by controlling the genes involved in normal development and functioning of the heart. Indirectly it also targets modifier genes and genes involved in signaling pathways. In this review, miRNAs involved in heart development, including dysregulation of miRNA which regulate various genes, modifiers and notch signaling pathway genes leading to cardiomyopathy are discussed. A study of these miRNAs would give an insight into the mechanisms involved in the processes of heart development and disease. Apart from this, information gathered from these studies would also generate suitable therapeutic targets in the form of antagomirs which are chemically engineered oligonucleotides used for silencing miRNAs.

Epistatic interactions in idiopathic pulmonary arterial hypertension.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene-gene interaction or epistasis and gene-environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes. AIM: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis. MATERIALS AND METHODS: A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene-gene interactions that increase the risk of IPAH. RESULTS: With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05. CONCLUSION: MDR method can be useful in understanding the role of epistatic and gene-environmental interactions in pathogenesis of IPAH.