My laboratory is interested in studying the genetic and epigenetic causes of Non-alcoholic fatty liver disease (NAFLD) in Indian populations. NAFLD is emerging as an important cause of liver disease in India, with a prevalence of 9% in rural India to 32% in the general population. NAFLD is an umbrella term which describes a range of related and progressive disorders, characterized by insulin resistance. The earliest stage of NAFLD is hepatic steatosis, which is characterized by the deposition of TG as lipid droplets in hepatocytes. Nonalcoholic steatohepatitis (NASH) is another stage of NAFLD characterized by hepatocyte injury, inflammation, and fibrosis. NASH, in turn, can progress to cirrhosis and hepatocellular carcinoma. NAFLD is a complex genomic disorder which is the hepatic manifestation of the metabolic syndrome.
In a recent, community-based epidemiological study of inhabitants of a rural area in West Bengal, the prevalence rates of NAFLD and cryptogenic cirrhosis were 8.7% and 0.2%, respectively. Surprisingly, these were low income lean individuals with mostly low or normal BMI. With continuous ongoing collection of epidemiological data in other parts of West Bengal, we are undertaking a genome-wide association analyses of NAFLD, which will complement our understanding of this novel Indian trait (perhaps a “Third world phenotype”), which is quite distinct from the Western phenotype, which is associated with obesity.
Recent results based on environmental and in vitro studies hypothesize a role for DNA methylation in the transcriptional control of key genes in liver disease. Epidemiologic evidence indicates that NAFLD in lean individuals might be a consequence of the transitional nutritional features/ malnutrition in these individuals. This observation points to the role of factors such as environment and lifestyle in determining the risk of disease, in addition to the genetic component. We think that these factors might have a huge influence on the methylome of these individuals, since only a subset of individuals develop NAFLD. Also, it is unclear whether NASH is an advanced stage of simple steatosis or if they are distinct patho-physiologies. Therefore, a second objective of my laboratory is to examine the roles that epigenetic factors play in NAFLD susceptibility and whether there is any interaction with genetic factors.
Projects: (extramurally funded) Genomic and Epigenomic analyses of Non Alcoholic Fatty Liver Disease (NAFLD) in the Indian population (funded by Dept. of Biotechnology)