Free Interleukin (IL)-18 levels, and the impact of IL18 and IL18BP genetic variation, in CHD patients and healthy men.
OBJECTIVE
To investigate free interleukin-18 (fIL-18) levels, and variation within the IL-18 system genes, in heart surgery patients, and healthy men.


RESULTS
fIL-18 was calculated from IL-18 and IL-18 binding protein (BP) levels, in 421 healthy men and 196 post-coronary artery bypass graft (CABG) patients. After surgery, fIL-18 peaked at 6 hours (from 117 to 331 pg/mL) but fell to below presurgery levels at 24 hours (99 pg/mL), because of changes in total IL-18 and IL-18BP. fIL-18 24 hours postsurgery was significantly higher in those who suffered a major complication after surgery (125 versus 80 pg/mL, P<0.01). Baseline total IL-18 was also higher in healthy men who went on to suffer an MI over 17 years of prospective study (276 versus 240 pg/mL, P=0.01). Tagging SNPs for IL18 (n=5) and IL18BP (n=3) were determined, in both studies the IL18 HapIII haplotype (frequency 30%) was associated with 36% lower baseline fIL-18 levels before surgery (P<0.01), and 7% lower in healthy men (P=0.04). The frequency of HapIII was lower in CABG patients than in healthy men (20.7 versus 29.8%, P<0.01).


CONCLUSIONS
IL-18 levels, which are determined in part by variation in IL18, play a role in CHD development and postsurgery outcome.
Thompson
Simon R
SR
Cardiovascular Genetics, Rayne Institute, University College London, WC1E 6JF, UK. rmhaseh@ucl.ac.uk.
Novick
Daniela
D
Stock
Carmel J
CJ
Sanders
Julie
J
Brull
David
D
Cooper
Jackie
J
Woo
Patricia
P
Miller
George
G
Rubinstein
Menachem
M
Humphries
Steve E
SE
D000368:Aged; D016022:Case-Control Studies; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics / Q000601:surgery; D005060:Europe; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein