Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction

Atherosclerosis. 2012 Apr;221(2):461-6. doi: 10.1016/j.atherosclerosis.2012.01.024. Epub 2012 Jan 20.

Abstract

Background: Major histocompatibility complex (MHC) gene region harbours haplotypes that associate with coronary artery disease (CAD). Their role in ST-elevation infarction (STEMI) or on the inflammatory level is not known.

Methods: Four candidate MHC markers were analyzed by real-time quantitative PCR and constructed into haplotypes from patients with STEMI (n = 162), matched controls with no CAD (n = 319) and general population sample (n = 149). High sensitivity C-reactive protein (hsCRP) was assessed in a follow-up visit from patients (n = 86) and at inclusion from other study subjects.

Results: The haplotype with one copy of HLA-DRB1*01, C4A, C4B but no HLA-B*35 doubled the risk of STEMI (OR = 2.15, 95%CI = 1.11-4.15, p = 0.020 for patients vs. controls, and OR = 2.26, 95%CI = 0.97-5.24, p = 0.052 for patients vs. population sample). The association between patients and controls persisted in multivariate analyses. The frequency of the haplotype was 5.86% (n = 19/324) in patients, 2.82% (n = 18/638) in controls and 2.68% (n = 8/298) in population sample. None of the individual MHC markers alone showed significant association with STEMI. In multivariate analyses, the haplotype carriers had higher hsCRP levels in patients (median 3.37 mg/L in carriers vs. 1.14 mg/L in non-carriers, p = 0.019) and in controls (median 2.90 mg/L vs. 1.21 mg/L, p = 0.009, respectively).

Conclusion: The MHC haplotype associates with STEMI and elevated baseline hsCRP levels. The results are in concordance with previous data on non-STEMI patients, implying that a HLA-DRB1*01--related haplotype increases the risk of CAD, possibly though increased inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Finland
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-DRB1 Chains / genetics*
  • Haplotypes*
  • Humans
  • Inflammation / blood
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation Mediators / blood
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / blood
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / immunology
  • Odds Ratio
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Risk Assessment
  • Risk Factors
  • Up-Regulation

Substances

  • Biomarkers
  • HLA-DRB1 Chains
  • HLA-DRB1*01 antigen
  • Inflammation Mediators
  • C-Reactive Protein