Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction.
OBJECTIVE
Several studies show that the inflammatory component in atherosclerosis may contribute to increased risk for cardiovascular disease (CVD). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-stimulatory cytokine of presumed importance for CVD and the metabolic syndrome.


RESULTS
In this case-control study, 1179 surviving myocardial infarction (MI) cases and 1528 healthy controls were genotyped for three IL-6 promoter SNPs, and serum concentrations of IL-6 and C-reactive protein (CRP) were measured. In men, MI risk assessed as odds ratios (OR) was higher with increasing IL-6 levels, with the highest compared to the lowest IL-6 quartiles giving an OR of 2.7 [95% CI 1.7-4.4]. The ORs were independent from the effects of elevated CRP which were associated with modest MI risks (OR = 1.6 [95% CI 1.0-2.5]). Also, synergistic interactions between high IL-6 levels and hypercholesterolaemia further increased MI risk estimates. The -174C allele was associated with lower serum-insulin levels among male controls but did not significantly influence MI risk or IL-6 levels.


CONCLUSIONS
Elevated IL-6 levels are important risk markers for MI in men, the risk being further enhanced through synergistic interaction with hypercholesterolaemia. The data provide no clear evidence that polymorphisms in the IL-6 promotor region play a significant role in the pathogenesis of MI, and it remains to be further evaluated whether or not the -174C allele is of relevance for insulin resistance.
Bennet
Anna M
AM
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, P.O. Box 210, S-171 77, Stockholm, Sweden. anna.bennet@imm.ki.se
Prince
Jonathan A
JA
Fei
Guo Zhong
GZ
Lyrenäs
Louise
L
Huang
YiHui
Y
Wiman
Björn
B
Frostegård
Johan
J
Faire
Ulf de
Ud
D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015994:Incidence; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate
D005819:Genetic Markers; D015850:Interleukin-6; D002097:C-Reactive Protein