Genetic predisposition in metabolic‐dysfunction‐associated fatty liver disease and cardiovascular outcomes—Systematic review

Abstract

Background: Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C > T near membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C > T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD. Materials and Methods: An electronic search on PubMed, Embase and Cochrane Library for articles published till 23 March 2020 was systematically performed. Articles were screened, and data extracted from eligible studies by two reviewers independently. Results: Studies conducted on adults with MAFLD involving European, Hispanic and African American populations evaluating rs641738 reported reduced hepatic expression of MBOAT7, increased hepatic fat content, severity of MAFLD, susceptibility to develop NASH, advanced fibrosis and HCC in adults. However, most articles involving Asian individuals contradicted these findings. Studies involving obese children associated rs641738 with increased plasma alanine aminotransferase (ALT) levels, while its association with MAFLD remains inconsistent. The rs641738 variant was assessed as a MAFLD susceptibility gene in coronary artery disease (CAD) reporting neutral effects. Conclusions: Despite inconclusive results in Asian populations, rs641738C > T near MBOAT7 is associated with increased hepatic fat, MAFLD severity, susceptibility to develop NASH, advanced fibrosis and HCC in adults from Caucasian, Hispanic and African American ethnicities with MAFLD, as well as elevated ALT levels in children, while exerting neutral effects in CAD.

rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis

“…The meta-analysis included 2,560 cases and 8,738 controls and found no evidence of an association between this variant and a diagnosis of NAFLD (Table S5). One previous systematic review 43 found positive associations between rs641738C>T in adults of Caucasian, Hispanic, and Black descent, with limited data in children (Table S5).…”

Nonalcoholic fatty liver disease or metabolic dysfunction‐associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches

“…Finally, in 2017, Liu et al tested the association of genotypes from the Human Exome Bead Chip with lipid levels and found that both TM6SF2 rs58542926 and PNPLA3 rs738409 variants were associated with lower lipid levels and a lower risk of CAD, but with an increased risk of steatosis and T2D 37 . Finally, the genetic variant rs641738C > T near MBOAT7 , predisposing to raised hepatic fat, MAFLD and susceptibility to develop NASH, did not associate with CAD risk 64 …”

NAFLD and Infection, a Nuanced Relationship

“…In some individuals, this seemingly benign fat accumulation in hepatocytes triggers inflammation leading to nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and/or development of hepatocellular carcinoma. e progression from NAFLD to these more severe entities is multifactorial and depends on an individual's genetic factors, environmental factors, and abnormal activation of the innate immune system [1][2][3][4][5]. Abnormal activation of the innate immune system leads to persistent low-grade inflammation which leads to tissue injury and fibrosis and has an important role in carcinogenesis [1][2][3][4][5].…”