Characterization of ALDH2-deficient alcohol-associated liver disease (duodenum RNA seq)

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme to detoxify the ethanol first metabolite acetaldehyde. Approximately 8% world population have inactive ALDH2 and have facial flushing due to high levels of acetaldehyde after alcohol consumption. Alcohol-associated liver disease (ALD) and hepatocellular carcinoma (HCC) in those with inactive ALDH2 have not been characterized. ALD pathogeneses in these individuals are likely very different from those with normal ALDH2, different diagnosis criteria and treatment are required for these two populations. Here we studied ALD in inactive Aldh2 knockin (Aldh2KI) mice with chronic ethanol feeding. Overall design: Male C57BL/6N and Aldh2KI mice aged 8 weeks were subjected to 1) Control diet for 8 weeks, 2) 2.5% ethanol diet for 8 weeks and gavaged with 2 g/kg ethanol twice per week (referred to as half diet), 3) 5% ethanol diet for 8 weeks and gavaged with 4 g/kg ethanol twice per week (referred to as full diet). Mice were euthanized 9 hours after the last ethanol gavage with an ethanol dose of 5 g/kg. Total RNA was extracted from duodenum using Trizol (Alkali Scientific, Fort Lauderdale, FL) and subjected to RNA seq.