title: Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease.
abstract: Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.
authors.affiliation: Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Palikhe
authors.forename: J
authors.initials: J
authors.lastname: Sinisalo
authors.forename: M
authors.initials: M
authors.lastname: Seppänen
authors.forename: V
authors.initials: V
authors.lastname: Valtonen
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: M L
authors.initials: ML
authors.lastname: Lokki
mesh_terms: D000328:Adult; D003324:Coronary Artery Disease / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged
chemical_list: D006680:HLA Antigens