MARC1 p.A165T polymorphism is associated with decreased liver injury and enhanced antioxidant activity in serum in patients with AIH

Background The progression of autoimmune hepatitis (AIH) varies between patients, which suggests the role of genetic modifiers. Genetic analyses of patients with fatty liver demonstrated protective effects of the MARC1p.A165T polymorphism. Here, we analyse MARC1, as well as the HSD17B13, PNPLA3, TM6SF2 and MBOAT7 variants in patients with AIH.

Methods The study cohort was composed of 313 non-transplanted adults with AIH, in addition a group of 30 patients who underwent liver transplantation for AIH was included in the analyses. The MARC1 (rs2642468), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926) and MBOAT7 (rs641738) SNPs were genotyped using TaqMan assays. Analysis of mitochondrial damage markers was conducted in relation to the MARC1 polymorphism.

Results MARC1 minor allele was associated with lower ALT (P = 0.04) and AST (P = 0.02). Among patients who were treated for AIH for at least 6 months, ones who carried the MARC1 variant had lower AST (P = 0.02), ALP and GGT (both P< 0.01), and lower APRI (P = 0.02). MARC1 genotype correlated with higher catalase (P = 0.02) and higher total antioxidant activity (P = 0.003) in serum. On the other hand, the PNPLA3polymorphism correlated MELD (P = 0.02) whereas MBOAT7 (rs641738) increased the odds of developing hepatocellular carcinoma (HCC) (OR 3.705, 95 %CI 1.22-11.28) during follow-up. None of the tested variants increased the risk of liver transplantation or death.

Conclusions Patients with AIH who carry the MARC1 polymorphism might exhibit a less pronounced liver injury which and improved resistance to oxidative stress. Genotyping of the MARC1, PNPLA3 and MBOAT7variants might help to stratify the risk of progressive AIH.

Publication History

Article published online:
07 September 2021