MRAS in coronary artery disease-Unchartered territory
Document Type
Article
Department
Biological and Biomedical Sciences
Abstract
Genome-wide association studies (GWAS) have identified coronary artery disease (CAD) susceptibility locus on chromosome 3q22.3. This locus contains a cluster of several genes that includes muscle rat sarcoma virus (MRAS). Common MRAS variants are also associated with CAD causing risk factors such as hypertension, dyslipidemia, obesity, and type II diabetes. The MRAS gene is an oncogene that encodes a membrane-bound small GTPase. It is involved in a variety of signaling pathways, regulating cell differentiation and cell survival (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase and phosphatidylinositol 3-kinase) as well as acute phase response signaling (tumor necrosis factor [TNF] and interleukin 6 [IL6] signaling). In this review, we will summarize the role of genetic MRAS variants in the etiology of CAD and its comorbidities with the focus on tissue distribution of MRAS isoforms, cell type/tissue specificity, and mode of action of single nucleotide variants in MRAS associated complex traits. Finally, we postulate that CAD risk variants in the MRAS locus are specific to smooth muscle cells and lead to higher levels of MRAS, particularly in arterial and cardiac tissue, resulting in MAPK-dependent tissue hypertrophy or hyperplasia.
Publication (Name of Journal)
IUBMB Life
DOI
https://doi.org/10.1002/iub.2805
Recommended Citation
Shah, P. W.,
Reinberger, T.,
Aherrahrou, Z.,
Erdmann, J.,
Hashmi, S.
(2024). MRAS in coronary artery disease-Unchartered territory. IUBMB Life.
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_bbs/1038
Comments
Volume, issue and pagination are not provided by the author/publisher.