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


CONCLUSIONS
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.
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. riitta.paakkanen@helsinki.fi
Riitta
R
Paakkanen
Marja-Liisa
ML
Lokki
Mikko
M
Seppänen
Ilkka
I
Tierala
Markku S
MS
Nieminen
Juha
J
Sinisalo
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016017:Odds Ratio; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
D015415:Biomarkers; D059811:HLA-DRB1 Chains; C497841:HLA-DRB1*01 antigen; D018836:Inflammation Mediators; D002097:C-Reactive Protein