Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease.
BACKGROUND
One of the most potent pro-inflammatory mediators is the early-acting cytokine interleukin (IL)-1, whose actions are regulated by the structurally related IL-1 receptor antagonist (IL-1 Ra). IL-1 Ra is a competitive IL-1 inhibitor and a powerful anti-inflammatory agent. Several autoimmune and inflammatory diseases have been associated with an allelic polymorphism of the IL-1 Ra gene.


METHODS
We investigated the frequency of allele 2 of an intron 2 polymorphism of the IL-1 Ra gene in 115 consecutive patients with ischemic heart disease -74 of which had a previous myocardial infarction (48 +/- 11 years), 21 chronic stable angina (54 +/- 10 years), and 20 unstable angina (54 +/- 9 years)--and in 80 healthy controls, matched for age and sex to patients with myocardial infarction (47 +/- 10 years). An 86 base pair variable tandem repeat in intron 2 of the IL-1 Ra gene was determined by a polymerase chain reaction-based method.


RESULTS
The frequency of allele 2 was 15% in controls (carriage rate 25%) and 17% in ischemic heart disease patients (carriage rate 28%; p = 0.70). The allele 2 frequency did not differ significantly among the three patient groups. Among patients with myocardial infarction, the allele 2 frequency tended to be higher in patients with myocardial infarction < 40 years compared to those > or = 40 years (20 vs 11%, p = 0.20, OR 1.85, 95% CI 0.70-4.90), and in patients with C-reactive protein levels > or = 3 mg/l compared to those with values < 3 mg/l (31 vs 16%, p = 0.15, OR 2.38, 95% CI 0.64-9.25).


CONCLUSIONS
These data do not show a clear-cut association between the allele 2 of this IL-1 Ra gene polymorphism and ischemic heart disease. Among patients with myocardial infarction, the increased allele 2 frequency in those of younger age and with higher levels of C-reactive protein merits further investigation.
Manzoli
A
A
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma.
Andreotti
F
F
Varlotta
C
C
Mollichelli
N
N
Verde
M
M
van de Greef
W
W
Sperti
G
G
Maseri
A
A
D000328:Adult; D000483:Alleles; D000787:Angina Pectoris / Q000235:genetics; D000789:Angina, Unstable / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins