Association of interleukin 8 with myocardial infarction: results from the Stockholm Heart Epidemiology Program.
BACKGROUND
Interleukin 8 (IL8) has been contradictorily associated with the risk of myocardial infarction (MI).


OBJECTIVE
To investigate the association of IL8 serum levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case control study, the Stockholm Heart Epidemiology Program.


RESULTS
IL8 levels (pg/mL) were divided into quartiles and the MI risk was calculated by logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T, rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and with MI risk. Multivariate adjusted ORs for MI risk by IL8 levels in the highest quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2-0.8) and men when compared to the lowest quartile. In female cases, IL8 levels decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2 genetic variants were not associated with IL8 levels. In men, the T allele at the IL8 SNP rs4073 was associated with a slight increase in the MI risk under an additive and a recessive model of inheritance.


CONCLUSIONS
IL8 serum levels were associated with a reduced occurrence of MI among women, whereas IL8 was associated with a slightly increased risk among men, possibly through different mechanisms. These data suggest that the biological effects of IL8 on MI risk may vary over time and warrant further cohort studies with repetitive IL8 measurements.
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: ilais.moreno.velasquez@ki.se.
Ilais Moreno
IM
Velásquez
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Paolo
P
Frumento
Division of Biochemistry, Department of Medical Biochemistry and Biophysics all at Karolinska Institutet, Stockholm, Sweden.
Katarina
K
Johansson
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Anita
A
Berglund
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Ulf
U
de Faire
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Karin
K
Leander
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Cardiovascular Medicine, Dept of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Bruna
B
Gigante
D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D060148:HapMap Project; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D023062:Receptors, Interleukin-8A / Q000235:genetics* / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
C508606:CXCL8 protein, human; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B
Atherosclerosis; Biomarker; Genetic variants; Interleukin 8; Myocardial infarction