Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography.
Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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http://orcid.org/0000-0002-9322-5545
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Wołkow
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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L
Drabik
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
J
J
Totoń-Żurańska
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
K
K
Kuś
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
J
J
Foryś
Institute of Neurology, Jagiellonian University Medical College, Krakow, Poland.
A
A
Słowik
Institute of Neurology, Jagiellonian University Medical College, Krakow, Poland.
J
J
Pera
Institute of Cardiology & John Paul II Hospital, Jagiellonian University Medical College, Krakow, Poland.
J
J
Godlewski
Institute of Cardiology & John Paul II Hospital, Jagiellonian University Medical College, Krakow, Poland.
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M
Tomala
Institute of Cardiology & John Paul II Hospital, Jagiellonian University Medical College, Krakow, Poland.
K
K
Żmudka
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
R
R
Olszanecki
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
J
J
Jawień
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
R
R
Korbut
D000368:Aged; D000483:Alleles; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D054400:Receptors, CCR7 / Q000235:genetics*; D012307:Risk Factors
C515370:CCR7 protein, human; D054400:Receptors, CCR7