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

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 ( = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD ( = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%). The genotype frequencies of 10 single nucleotide polymorphisms (SNPs) were analyzed.

RESULTS

The genotype GG and genotype GG were observed more frequently, and the percentage of patients with the genotype GG was lower in ALD compared with NAFLD patients (, 16 4%; 84 44%; 62 72%, respectively; all  < 0.01). Comparing noncirrhosis to cirrhosis, the frequency of the potassium voltage-gated channel subfamily Q member 1 () genotype TT and adrenoceptor beta 3 () genotype TT was increased significantly in ALD-related cirrhosis. In contrast, the patatin-like phospholipase 3 () genotype CC was decreased significantly in NAFLD-related cirrhosis. A comparison of patients with and without HCC demonstrated that the genotype TT was increased significantly in both HCC groups. In addition, associations between the genotype GG and ALD-HCC and the G allele of 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.