Background: Disease risk variants are likely to affect gene expression in a context- and cell-type specific manner. The membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs8736 metabolic-dysfunction-associated fatty liver disease (MAFLD)-risk variant was recently reported to be a negative regulator of toll-like receptors (TLRs) signalling in macrophages. Whether this effect is generic or cell-type specific in immune cells is unknown.
Methods: We investigated the impact of modulating TLR signaling on MBOAT7 expression in peripheral blood mononuclear cells (PBMCs). We also examined whether the rs8736 polymorphism in MBOAT7 regulates this effect. Furthermore, we measured the allele-specific expression of MBOAT7 in various immune cell populations under both unstimulated and stimulated conditions.
Results: We show that MBOAT7 is down-regulated by TLRs in PBMCs. This effect is modulated by the rs8736 polymorphism. Additionally, we provide evidence that MBOAT7 acts primarily as a modulator of TLR signalling in mononuclear phagocytes.
Conclusion: Our results highlight the importance of studying Genome-Wide Association Studies (GWAS) signals in the specific cell types in which alterations of gene expression are found.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.31083/j.fbl2904148 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.
J Clin Exp Hepatol
April 2024
Internal Medicine Department, Medical Research and Clinical Studies Institute, 33 El Buhouth St, Ad Doqi, Dokki, Cairo Governorate 12622, Egypt.
Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies.
View Article and Find Full Text PDFA Cell Specific Effect of MBOAT7 MAFLD-risk Variant on Immune Cells.
Front Biosci (Landmark Ed)
April 2024
Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW 2145, Australia.
Background: Disease risk variants are likely to affect gene expression in a context- and cell-type specific manner. The membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs8736 metabolic-dysfunction-associated fatty liver disease (MAFLD)-risk variant was recently reported to be a negative regulator of toll-like receptors (TLRs) signalling in macrophages. Whether this effect is generic or cell-type specific in immune cells is unknown.
View Article and Find Full Text PDFGenetic Predictors of Comorbid Course of COVID-19 and MAFLD: A Comprehensive Analysis.
Viruses
August 2023
Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine.
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.
View Article and Find Full Text PDFA metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes.
Nat Commun
December 2022
Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
The breakdown of toll-like receptor (TLR) tolerance results in tissue damage, and hyperactivation of the TLRs and subsequent inflammatory consequences have been implicated as risk factors for more severe forms of disease and poor outcomes from various diseases including COVID-19 and metabolic (dysfunction) associated fatty liver disease (MAFLD). Here we provide evidence that membrane bound O-acyltransferase domain containing 7 (MBOAT7) is a negative regulator of TLR signalling. MBOAT7 deficiency in macrophages as observed in patients with MAFLD and in COVID-19, alters membrane phospholipid composition.
View Article and Find Full Text PDFGenetic variants associated with metabolic dysfunction-associated fatty liver disease in western China.
J Clin Lab Anal
September 2022
Department of General Practice, West China Hospital, Sichuan University, Chengdu, China.
Article Synopsis
- The study investigated the relationship between specific genetic variants (SNPs) and metabolic dysfunction-associated fatty liver disease (MAFLD) in a population in western China.
- A total of 536 participants (286 with MAFLD and 250 healthy) were analyzed for multiple SNPs using logistic and linear regression to evaluate their association with MAFLD and related laboratory characteristics.
- Although some initial associations were observed, particularly with PNPLA3 and GCKR variants, these were not statistically significant after adjusting for multiple comparisons, leading to the conclusion that there is no strong link between these SNPs and MAFLD risk in this population.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!