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Significant roles of potential genes and their mutations in nonalcoholic fatty liver disease.

ABSTRACT: In addition to having inflammation in the liver, overweight people also have changes in the composition of their immune systems and subsets of their immune systems. There are several genes involved in liver metabolism that have been implicated in nonalcoholic fatty liver disease (NAFLD), a liver disease associated with obesity, which is caused by high triglycerides and liver transaminases. NAFLD, a global liver disease, may differ in gene expression depending on where a person lives. In some alleles, the risk factors were independent. Finally, the researchers identified many genetic variations connected to fatty liver disease in those who did not drink alcohol regularly. These variants were located in genes involved in RNA metabolism, protein catabolism, and energy metabolism.

SUBMITTER: Sokouti B

PROVIDER: S-EPMC10369655 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Significant roles of potential genes and their mutations in nonalcoholic fatty liver disease.

Sokouti Babak B

Clinical and experimental hepatology 20230621 2

In addition to having inflammation in the liver, overweight people also have changes in the composition of their immune systems and subsets of their immune systems. There are several genes involved in liver metabolism that have been implicated in nonalcoholic fatty liver disease (NAFLD), a liver disease associated with obesity, which is caused by high triglycerides and liver transaminases. NAFLD, a global liver disease, may differ in gene expression depending on where a person lives. In some all ...[more]

PMID: 37502439

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Project description:Coronary artery disease (CAD) is the principal cause of death in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to investigate whether NAFLD is causally involved in the pathogenesis of CAD. For this, previously reported NAFLD susceptibility genes were clustered and tested for an association with CAD in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis plus the Coronary Artery Disease Genetics (CARDIoGRAMplusC4D) Consortium data set. The role of plasma lipids as a potential mediator was explored by using data from the Global Lipids Genetics Consortium. Statistical analyses revealed that the combination of 12 NAFLD genes was not associated with CAD in 60,801 CAD cases and 123,504 controls (odds ratio [OR] per NAFLD risk allele, 1.0; 95% confidence interval [CI], 0.99-1.00). In a subsequent sensitivity analysis, a positive relationship was observed after exclusion of gene variants that are implicated in NAFLD through impaired very low-density lipoprotein secretion (i.e., microsomal triglyceride transfer protein [MTTP], patatin-like phospholipase domain containing 3 [PNPLA3], phosphatidylethanolamine N-methyltransferase [PEMT], and transmembrane 6 superfamily member 2 [TM6SF2]) (OR, 1.01; 95% CI, 1.00-1.02). Clustering of the excluded genes showed a significant negative relationship with CAD (OR, 0.97; 95% CI, 0.96-0.99). A substantial proportion of the observed heterogeneity between the individual NAFLD genes in relation to CAD could be explained by plasma lipids, as reflected by a strong relationship between plasma lipids and CAD risk conferred by the NAFLD susceptibility genes (r = 0.76; P = 0.004 for low-density lipoprotein cholesterol). Conclusion: NAFLD susceptibility genes do not cause CAD per se. The relationship between these genes and CAD appears to depend to a large extent on plasma lipids. These observations strongly suggest taking plasma lipids into account when designing a new drug to target NAFLD.

Dataset Information

Significant roles of potential genes and their mutations in nonalcoholic fatty liver disease.

Publications

Significant roles of potential genes and their mutations in nonalcoholic fatty liver disease.

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