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MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery.

Piotr KalinowskiWiktor SmykMałgorzata NowosadRafał PaluszkiewiczŁukasz MichałowskiBogna Ziarkiewicz-WróblewskaSusanne N WeberPiotr MilkiewiczFrank LammertKrzysztof ZieniewiczMarcin Krawczyk
Published in: International journal of molecular sciences (2022)
The severity of hepatic steatosis is modulated by genetic variants, such as patatin-like phospholipase domain containing 3 ( PNPLA3 ) rs738409, transmembrane 6 superfamily member 2 ( TM6SF2 ) rs58542926, and membrane-bound O-acyltransferase domain containing 7 ( MBOAT7 ) rs641738. Recently, mitochondrial amidoxime reducing component 1 ( MTARC1 ) rs2642438 and hydroxysteroid 17-beta dehydrogenase 13 ( HSD17B13 ) rs72613567 polymorphisms were shown to have protective effects on liver diseases. Here, we evaluate these variants in patients undergoing bariatric surgery. A total of 165 patients who underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies and 314 controls were prospectively recruited. Genotyping was performed using TaqMan assays. Overall, 70.3% of operated patients presented with hepatic steatosis. NASH (non-alcoholic steatohepatitis) was detected in 28.5% of patients; none had cirrhosis. The increment of liver fibrosis stage was associated with decreasing frequency of the MTARC1 minor allele ( p = 0.03). In multivariate analysis MTARC1 was an independent protective factor against fibrosis ≥ 1b (OR = 0.52, p = 0.03) and ≥ 1c (OR = 0.51, p = 0.04). The PNPLA3 risk allele was associated with increased hepatic steatosis, fibrosis, and NASH (OR = 2.22, p = 0.04). The HSD17B13 polymorphism was protective against liver injury as reflected by lower AST ( p = 0.04) and ALT ( p = 0.03) activities. The TM6SF2 polymorphism was associated with increased ALT ( p = 0.04). In conclusion, hepatic steatosis is common among patients scheduled for bariatric surgery, but the MTARC1 and HSD17B13 polymorphisms lower liver injury in these individuals.
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