Common MARC1 and HSD17B13 polymorphism have protective effects on liver injury in obese patients undergoing bariatric surgery

Background The severity of liver steatosis is modulated by the PNPLA3 p.I148M, TM6SF2 rs58542926 and MBOAT7 rs641738 polymorphisms. Recently two genetic variants, namely MARC1 rs2642438 and HSD17B13 rs72613567, were shown to have protective effects in patients with chronic liver diseases. Here we analyse these variants in patients undergoing bariatric surgery.

Methods A total of 165 obese individuals (mean BMI 43.8 kg/m2) who underwent laparoscopic sleeve gastrectomy were prospectively recruited. Genotyping of the MARC1, PNPLA3, TM6SF2, MBOAT7 and HSD17B13 polymorphisms was performed using TaqMan assays. Liver biopsies were performed intraoperatively in all patients.

Results Overall, 70.3% of operated patients had hepatic steatosis but none had cirrhosis at liver biospy. The MARC1 minor allele had protective effects on hepatic fibrosis whilst variant PNPLA3 increased the risk of developing steatosis and fibrosis as well as non-alcoholic steatohepatitis (NASH) and was associated with higher serum glucose. On the other hand, the harmful effects of the PNPLA3 p.I148M variant were lower among carriers of the MARC1 polymorphism. Multivariate analysis showed that variant MARC1 was an independent protective factor against liver fibrosis. The HSD17B13 polymorphism was protective against liver injury as reflected by lower AST and ALT activities. The TM6SF2 polymorphism was associated with increased risk for S3 steatosis and increased serum ALT.

Conclusion Hepatic steatosis is frequent among obese patients but presence of the MARC1 and HSD17B13 polymorphisms lowers liver injury in these individuals. Of note, variant MARC1 reduces the harmful effects of the major genetic risk factor for progressive fatty liver, namely PNPLA3 p.I148M.

Publication History

Article published online:
26 January 2022