Inflammation and coronary artery disease: insights from genetic studies.
Recent genome-wide association studies (GWASs) have provided a vast amount of new information relevant to the myriad of biological pathways related to atherosclerosis and its progression. Although atherosclerosis is a complex process, both GWASs and candidate gene studies add support to the hypothesis that proinflammatory pathways, involving both innate and adaptive immunity, play a causal role in coronary artery disease (CAD) and its clinical manifestations. Recent GWASs have identified several inflammation-related loci associated with CAD risk. These include CXCL2, encoding an atheroprotective chemokine, and a region near HLA-C in the major histocompatibility locus on chromosome 6p21. The ABO locus, also linked to CAD risk by the GWAS approach, is related to multiple phenotypes, including plasma interleukin-6 (IL-6) levels. Finally, relevant to inflammation, the 9p21 CAD risk locus appears to play a role in interferon-gamma signalling. Candidate gene studies also support a causative role of inflammation pathways in atherosclerosis. Of note, a common loss of function coding variant in the IL-6 receptor gene (IL6R) is associated with a reduction in CAD risk.
University of Ottawa Heart Institute, Ottawa, Ontario, Canada. rmcpherson@ottawaheart.ca
Ruth
R
McPherson
Robert W
RW
Davies
D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D015415:Biomarkers; D015236:HLA-C Antigens