• Agostino Di Ciaula, Leonilde Bonfrate, Harshitha Shanmugam, Susanne N Weber, Marcin Krawczyk, and Piero Portincasa.
• Clinica Medica "A. Murri", Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari "Aldo Moro" Medical School, Bari, Italy.
• Eur. J. Clin. Invest. 2023 Aug 1; 53 (8): e14003e14003.

BackgroundMBOAT7 rs641738 variant is a risk factor for nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, but the relationship between this polymorphism and early liver dysfunction remains uncertain.MethodsEighty outpatients underwent blood analyses, liver imaging by ultrasound and acoustic radiation force impulse shear wave elastography and were genotyped for MBOAT7 (wild-type [WT], rs641738 heterozygous or homozygous) polymorphism using TaqMan assays.ResultsNAFLD was confirmed in 53 patients. Portal uptake and hepatocyte microsomal metabolization of (13 C)-methacetin were explored by measuring 13 CO2 appearance in exhaled air. The distribution of the MBOAT7 genotypes was comparable in subjects with or without NAFLD. The majority of subjects with or without NAFLD had fibrosis ≤ F1 but decreased portal extraction of (13 C)-methacetin, i.e. 78.6% in homozygous, 45.0% in heterozygous and 46.2% in WT for the MBOAT7 variant. Both substrate extraction and microsomal metabolization were mostly defective in the homozygous carriers. The extraction efficiency from portal blood flow was minimal in subjects with both homozygous rs641738 polymorphism and NAFLD, as compared to those with WT/heterozygous polymorphism, with or without NAFLD.ConclusionsThe homozygous MBOAT7 rs641738 polymorphism per se is associated with a reduced extraction efficiency of (13 C)-methacetin from the portal flow pointing to subclinical liver dysfunction independently from liver fibrosis. Liver steatosis worsens (13 C)-methacetin extraction efficiency. We urge to better explore the mechanisms of interaction between external factors and multiple gene polymorphisms (including MBOAT7), paving the road to primary prevention and novel therapeutic strategies.© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

19 keywords...

hide…