Studies on NAFLD and impact of environmental factors

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a significant public health issue, and its frequency has risen in recent years. NAFLD refers to a group of disorders characterized by a buildup of fat in the liver. It is most commonly found in those who are overweight or obese. This thesis will use the distribution of genetic polymorphisms within NAFLD and control populations to answer a number of questions, including whether SNPs associated with a change in function of associated genes could perform natural experiments on disease progression, the role of environmental co-factors, the efficacy of therapeutic targets, and disease association mechanisms. This thesis also aims to identify the association between NAFLD risk and CVD risk in Scottish populations. Using the GODARTs Scottish cohort (longitudinal). In GoDARTs, genotypic and biochemistry data were available for 13,150 patients. We evaluated the role of the CYP2E1 gene, as well as biochemical and anthropometric parameters for their association with NAFLD in the GODARTs cohort. We found some candidate genes for CYP2E1, and environmental factors predispose to non-alcoholic fatty liver disease. In addition, we found the CYP2E1 polymorphism rs2249695 was positively associated with ALD. In IL-6 and IL-6R polymorphisms to interact with NAFLD in determining CVD risk, we did not find an association between them in the GODARTs cohort. The work presented in this thesis highlights the worth of employing a large population dataset to investigate the distribution of genetic polymorphisms in NAFLD and control populations, as well as the relevance of environmental co-factors, therapeutic efficacy, and mechanisms of disease association.