MRAS in coronary artery disease —Unchartered territory

AbstractGenome-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). CommonMRAS variants are also associated with CAD causing risk factors such as hypertension, dyslipidemia, obesity, and type II diabetes. TheMRAS 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 geneticMRAS variants in the etiology of CAD and its comorbidities with the focus on tissue distribution ofMRAS isoforms, cell type/tissue specificity, and mode of action of single nucleotide variants inMRAS associated complex traits. Finally, we postulate that CAD risk variants in theMRAS locus are specific to smooth muscle cells and lead to higher levels ofMRAS, particularly in arterial and cardiac tissue, resulting in MAPK-dependent tissue hypertrophy or hyperplasia.
Source: IUBMB Life - Category: Research Authors: Tags: CRITICAL REVIEW Source Type: research