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Molecular Genetics of Cardiovascular Diseases.Cardiovascular diseases (coronary heart disease, heart failure, stroke etc.) affect a large section of the adult population and are the leading causes of morbidity and mortality in many countries including India. Recent studies have documented that although the mortality associated with cardiovascular diseases are declining in the developed countries including Western Europe and North America, the burden of cardiovascular diseases continues to rise in the developing countries including India. Notably, South Asians have a greater prevalence of cardiovascular risk factors than the rest of the World, and India itself is estimated to have more than half of the World's heart disease patients at present. These diseases not only cause enormous loss of human lives, but also lead to huge health care cost, tremendous economic and social burden, declining national productivity and quality of life.
The determinants of cardiovascular diseases are multi-factorial, complex and often interrelated. We are interested to understand the molecular and genetic bases of hypertension (elevated arterial blood pressure) because it is the chief risk factor for cardiovascular diseases. Despite extensive research over the past couple of decades, the pathogenesis of hypertension is only partially understood. Besides environmental factors (such as stress, inadequate physical activity, smoking/tobacco use and unhealthy diet that includes higher dietary fats/higher sodium/lower fruits and vegetables), strong influences of genes have been reported. Moreover, hypertension may be associated with and complicated by dyslipidemia (elevated levels of LDL-cholesterol and triglycerides and reduced level of HDL-cholesterol in the circulation), a major risk factor for cardiovascular diseases. In addition, diabetes mellitus is another major risk factor for cardiovascular diseases. Indeed, more than 65% of people with diabetes mellitus die of some form of heart disease/stroke and heart disease death rates in adults with diabetes are at least two times higher as compared to those without diabetes. Therefore, we are also interested to unravel the genetic and molecular mechanisms that govern the pathogenesis of lipid disorder and type 2 diabetes.
Our experimental approach involves identification, transcriptional and post-transcriptional regulation of the candidate/susceptibility genes for hypertension and related cardiovascular disease states. We also study the roles of translated protein products of the candidate genes in disease pathogenesis. Additionally, we work on discovering naturally-occurring functional genetic variants (single nucleotide polymorphisms and haplotypes) that may act as risk factors for development of cardiovascular diseases. We investigate at the cellular level (employing cultured cell lines), utilize animal models (genetically modified rodents) and human subjects (cases versus controls) for our various studies. Results from these studies are likely to shed light on the molecular mechanisms and ultimately help to develop diagnostic and therapeutic strategies for management of the cardiovascular diseases.