Genetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis

Viruses. 2023 Aug 12;15(8):1724. doi: 10.3390/v15081724.


Metabolic-associated fatty liver disease (MAFLD) and its potential impact on the severity of COVID-19 have gained significant attention during the pandemic. This review aimed to explore the genetic determinants associated with MAFLD, previously recognized as non-alcoholic fatty liver disease (NAFLD), and their potential influence on COVID-19 outcomes. Various genetic polymorphisms, including PNPLA3 (rs738409), GCKR (rs780094), TM6SF2 (rs58542926), and LYPLAL1 (rs12137855), have been investigated in relation to MAFLD susceptibility and progression. Genome-wide association studies and meta-analyses have revealed associations between these genetic variants and MAFLD risk, as well as their effects on lipid metabolism, glucose regulation, and liver function. Furthermore, emerging evidence suggests a possible connection between these MAFLD-associated polymorphisms and the severity of COVID-19. Studies exploring the association between indicated genetic variants and COVID-19 outcomes have shown conflicting results. Some studies observed a potential protective effect of certain variants against severe COVID-19, while others reported no significant associations. This review highlights the importance of understanding the genetic determinants of MAFLD and its potential implications for COVID-19 outcomes. Further research is needed to elucidate the precise mechanisms linking these genetic variants to disease severity and to develop gene profiling tools for the early prediction of COVID-19 outcomes. If confirmed as determinants of disease severity, these genetic polymorphisms could aid in the identification of high-risk individuals and in improving the management of COVID-19.

Keywords: COVID-19; GCKR; LYPLAL1; MAFLD; NAFLD; PNPLA; SARS-CoV-2; TM6SF2; rs12137855; rs58542926; rs738409; rs780094.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / epidemiology
  • COVID-19* / genetics
  • Comorbidity
  • Genome-Wide Association Study
  • Humans
  • Lipid Metabolism
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Non-alcoholic Fatty Liver Disease* / genetics

Grants and funding

RECOOP Grant #36—CSMC Senior Scientists (RCSS) “Comprehensive Analysis of Genetic Predictors for MAFLD Development in patients with COVID-19”.