The potential role of genes in nonalcoholic fatty liver disease.

Although most people with obesity and type 2 diabetes will have steatosis, only a minority will ever develop nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Family studies suggest that genetic factors are important in disease progression, although dissecting genetic factors playing a role in NASH and fibrosis from those influencing the development established risk factors is difficult. Several approaches can be used to look for genetic factors playing a role in nonalcoholic fatty liver disease (NAFLD). In the future, genome-wide single nucleotide polymorphism (SNP) scanning of cases and controls may become feasible. To date, however,studies have relied on candidate gene, case control, allele association methodology. Recent, and as yet preliminary, studies have reported associations between steatosis severity, NASH, and fibrosis with genes whose products are involved in lipid metabolism,oxidative stress, and endotoxin-cytokine interactions. If confirmed,these associations will enhance understanding of disease pathogenesis,and accordingly, the ability to design effective therapies.