IL-18 gene polymorphism, cardiovascular mortality and coronary artery disease.
BACKGROUND
Interleukin 18(IL-18) is a pro-atherosclerotic cytokine. Elevated IL-18 levels and the genetic variation of the IL-18 have been previously linked with acute coronary events and cardiovascular mortality among patients with coronary artery disease (CAD). We studied the possible association between the IL-18 gene polymorphism and cardiovascular mortality during follow-up among Finnish patients who had undergone a clinical exercise stress test, in addition to the possible effect on the expression of angiography-verified CAD.


METHODS
A total of 2152 patients of the Finnish Cardiovascular Study (cohort study) were followed up for 6·3years and cardiovascular mortality was recorded. Angiography was performed on 461 patients. Genotyping of five common single nucleotide polymorphisms (SNPs) of the IL-18 gene was performed using the 5'nuclease assay for allelic discrimination with the ABI Prism 7900HT Sequence Detection System.


RESULTS
Among the study population, IL-18 gene polymorphism did not associate with cardiovascular mortality. According to adjusted binary regression analysis, the male carriers of one major haplotype (the only ones carrying the t allele of the +127 C/t SNP) had a lower occurrence rate for significant CAD defined as > 50% stenosis in at least one of the main branches of the coronary arteries (OR 0·495, 95% CI 0·862-0·284, P=0·041). No associations were observed among women. The sex-by-genotype interaction was significant (P=0·033).


CONCLUSIONS
The IL-18 gene was not found to associate significantly with mortality. Among patients who had coronary angiography, one major haplotype of the IL-18 gene has a gender-dependent different impact on the expression of CAD.
Hernesniemi
Jussi A
JA
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland Medical School, University of Tampere, Tampere, Finland. jussi.hernesniemi@uta.fi
Anttila
Kaisa
K
Nieminen
Tuomo
T
Kähönen
Mika
M
Mononen
Nina
N
Nikus
Kjell
K
Turjanmaa
Väinö
V
Viik
Jari
J
Lehtinen
Rami
R
Lehtimäki
Terho
T
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics* / Q000401:mortality; D016009:Chi-Square Distribution; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D044465:White People / Q000235:genetics
D020382:Interleukin-18