Genetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease

Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

“…Among the emerging newly discovered risk loci, variants near the genes encoding for membrane bound O acyltransferase domain containing 7 (MBOAT7) and transmembrane channel like 4 (TMC4) have been shown to be associated with development and severity of NAFLD in patients of European descent 101 . Similarly, within the Latino popu lation in South America, the TM6SF2 Glu167Lys and PNPLA3 Ile148Met protein variants seem to confer susceptibility to progressive NASH 102 .…”

Baseline Parameters in Clinical Trials for Nonalcoholic Steatohepatitis: Recommendations From the Liver Forum

“…9 These variants have specific ethnic distributions, with PNPLA3 accounting for ≤72% of interethnic variation in hepatic triglyceride content in the Dallas Heart Study. 10 DNA (venous blood or extracted from tissue) should be collected and the informed consent process should include the ability to genotype these candidate genes as well as “genome-wide” analyses for future analysis.…”

Genetics of alcoholic liver disease and non-alcoholic steatohepatitis

“…This increases to 3.37-fold in ARLD patients that are homozygous for the I148M minor allele. 12 The relationship between PNPLA3 rs738409 and progressive ARLD has been further replicated in a European GWAS, with independent validation. 7 Further to its association with ARLD and NAFLD, PNPLA3 rs738409 has been reported to be a susceptibility variant for hepatocellular carcinoma (HCC).…”

“…12 The best replicated association with genes involved in alcohol metabolism and ARLD are variants in the alcohol metabolising enzymes alcohol dehydrogenase and acetaldehyde dehydrogenase. Variants in these genes lead to an inability to remove a toxic product of alcohol metabolism -acetaldehyde.…”