Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction.
Inflammation plays an important role in the pathogenesis of atherosclerosis and acute coronary syndromes. Cytokines IL-10 and TNF-alpha exert opposite functions in inflammatory reactions, IL-10 acting predominantly as an antiinflammatory and TNF-alpha as a proinflammatory factor. Functional single nucleotide polymorphisms in the genes of IL-10, TNF-alpha, and TNF-beta are associated with gene expression and plasma levels of IL-10 and TNF-alpha. The aim of the study was to assess whether these IL-10 and TNF gene polymorphisms are related to the risk of coronary artery disease (CAD) and myocardial infarction (MI). Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n=998) and patients with old or acute MI constituted the group with MI (n=793). Subjects with neither angiographic CAD nor symptoms or signs of MI (n=340) served as controls. They were matched with the patients for age and sex. Genotyping was performed with techniques based on the polymerase chain reaction. Allele frequencies, genotype distributions, and frequencies of allele combinations for three IL-10 promoter polymorphisms, -1082G/A, -819C/T and -592C/A, were similar between CAD patients, MI patients, and matched controls. Similarly, genetic analysis did not reveal group-specific differences for the TNF-alpha promoter polymorphisms -863C/A and -308G/A, as well as for the TNF-beta intron 1 polymorphism 252G/A. In addition, no relationship was found between specific combinations of IL-10 and TNF alleles, indicative of low IL-10 and high TNF-alpha production, respectively, and CAD or MI. The lack of association persisted also after adjusting for other cardiovascular risk factors. Our findings suggest that six different and functionally relevant polymorphisms of the genes coding for IL-10, TNF-alpha, and TNF-beta are neither separately nor in cooperation associated with the risk of CAD or MI in angiographically examined patients.
Koch
W
W
Deutsches Herzzentrum München and 1 Medizinische Klinik rechts der Isar, Technische Universität München, Munich, Germany. wkoch@dhm.mhn.de
Kastrati
A
A
Böttiger
C
C
Mehilli
J
J
von Beckerath
N
N
Schömig
A
A
D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10