Decreased risk for myocardial infarction and lower tumor necrosis factor-alpha levels in carriers of variants of the PDCD1 gene.
Increasing interest has been directed toward the inflammatory mechanisms involved in the pathogenesis of myocardial infarction (MI). In the search for genetic mechanisms underlying these inflammatory components, we studied variants of programmed cell death-1 (PDCD1), an immunoinhibitory receptor that inhibits lymphocyte activation and cytokine production, previously shown to be associated with several autoimmune disorders. The PD1.1, PD1.3, and PD1.6 polymorphisms of the PDCD1 gene were typed in the Stockholm Heart Epidemiology Program, a population-based clinical material consisting of 1179 first-time MI case patients and 1528 unaffected control subjects. Individual alleles and haplotypes were studied for association with levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and C-reactive protein and risk for MI. We observed a weak protective effect of PD1.3A allele for MI (odds ratio: 0.78, 95% confidence interval: 0.61-0.98). We also observed decreased levels of TNF-alpha in carriers of the PD1.1A/PD1.3G/PD1.6A haplotype, which is consistent with our previous observation that this haplotype may be protective from autoimmune conditions. Carriers of variants of the PDCD1 gene exhibit a decreased risk for nonfatal myocardial infarction, and PDCD1 mediates variation in TNF-alpha levels.
Bennet
Anna M
AM
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. Anna.Bennet@ki.se
Alarcón-Riquelme
Marta
M
Wiman
Björn
B
de Faire
Ulf
U
Prokunina-Olsson
Ludmila
L
D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D061026:Programmed Cell Death 1 Receptor; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D015850:Interleukin-6; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein