Differences in the genetic backgrounds of patients with alcoholic liver disease and non-alcoholic fatty liver disease

Abstract

Background and Aim: Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD. Methods: This study enrolled 318 Japanese patients with ALD (n = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD (n = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%). The genotype frequencies of 10 single nucleotide polymorphisms (SNPs) were analyzed. Results: The ADH1B genotype GG and ALDH2 genotype GG were observed more frequently, and the percentage of patients with the MTP genotype GG was lower in ALD compared with NAFLD patients (ADH1B, 16 vs 4%; ALDH2 84 vs 44%; MTP 62 vs 72%, respectively; all P < 0.01). Comparing noncirrhosis to cirrhosis, the frequency of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) genotype TT and adrenoceptor beta 3 (ADRB3) genotype TT was increased significantly in ALD-related cirrhosis. In contrast, the patatin-like phospholipase 3 (PNPLA3) genotype CC was decreased significantly in NAFLD-related cirrhosis. A comparison of patients with and without HCC demonstrated that the KCNQ1 genotype TT was increased significantly in both HCC groups. In addition, associations between the KCNJ15 genotype GG and ALD-HCC and the G allele of PNPLA3 and NAFLD-HCC were identified. Conclusions: SNPs in genes related to ethanol and lipid metabolism clearly differed between patients with ALD and NAFLD. KCNQ1 might affect the progression and hepatocarcinogenesis in both ALD and NAFLD.