W. Koch et al., Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction, ATHEROSCLER, 159(1), 2001, pp. 137-144
Citations number
56
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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 anti
inflammatory and TNF-alpha as a proinflammatory factor. Functional single n
ucleotide polymorphisms in the genes of IL-10, TNF-alpha and TNF-beta are a
ssociated with gene expression and plasma levels of IL-10 and TNF-alpha. Th
e aim of the study was to assess whether these IL-10 and TNF gene polymorph
isms are related to the risk of coronary artery disease (CAD) and myocardia
l infarction (MI). Consecutive, angio graphically examined patients with si
gnificant coronary stenoses but without symptoms or signs of old or acute M
I constituted the group with CAD (n = 998) and patients with old or acute M
I constituted the group with MI (n = 793). Subjects with neither angiograph
ic 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 te
chniques based on the polymerase chain reaction. Allele frequencies, genoty
pe distributions, and frequencies of allele combinations for three IL-10 pr
omoter polymorphisms, - 1082G/A, -819C/T and -592C/A, were similar between
CAD patients, MI patients, and matched controls. Similarly, genetic analysi
s did not reveal group-specific differences for the TNF-alpha promoter poly
morphisms -863C/A and -308G/A, as well as for the TNF-beta intron I polymor
phism 252G/A. In addition, no relationship was found between specific combi
nations of IL-10 and TNF alleles, indicative of low IL-10 and high TNF-alph
a production, respectively, and CAD or MI. The lack of association persiste
d also after adjusting for other cardiovascular risk factors. Our findings
suggest that six different and functionally relevant polymorphisms of the g
enes coding for IL-10, TNF-alpha, and TNF-beta are neither separately nor i
n cooperation associated with the risk of CAD or angiographically examined
patients. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.