Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty.
BACKGROUND
Percutaneous transluminal coronary angioplasty (PTCA) is limited by the recurrence of luminal stenosis, which occurs in up to 50% of procedures. It has been shown that patient specific factors, perhaps genes, contribute to this process.


OBJECTIVE
To determine whether completion of healing after PTCA is part of an acute self limiting inflammatory process and whether polymorphism at important inflammatory gene loci might determine susceptibility to restenosis after PTCA.


METHODS
DNA samples were collected from 171 patients attending for elective PTCA in Sheffield (S) and Leicester (L), who were scheduled to undergo follow up angiography (at four months (L) or six months (S)) as part of other restenosis studies. At follow up angiography, the patients were separated into restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loci (IL-1A (-889), IL-1B (-511), IL-1B (+3954), and IL-1RN intron 2 VNTR (variable number tandem repeat)) were genotyped using methods based on polymerase chain reaction. Significance was assessed by chi(2) analysis of the relevant contingency table, and the magnitude of effect was estimated by calculating odds ratios. The Mantel-Haenszel (MH) test was applied to summarise data across the two populations.


RESULTS
Allele 2 at IL-1RN (IL-1RN*2) was significantly over represented in the non-restenoser group (L+S, 34% v 23% in restenosers). Furthermore, IL-1RN*2 homozygosity was increased in the non-restenoser population compared with the restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, single vessel disease only), and the effect seemed to be restricted to the single vessel disease subpopulation. For other polymorphism within IL-1 related loci no significant associations were found with either restenosis or non-restenosis.


CONCLUSIONS
IL-1RN*2 may be associated with protection from restenosis after PTCA for individuals with single vessel disease. As this polymorphism has functional significance, this finding suggests that alteration in an individual's inflammatory predisposition may modulate the blood vessel response to injury.
Francis
S E
SE
Cardiovascular Medicine Group, Division of Clinical Sciences, Clinical Sciences Centre, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, UK.
Camp
N J
NJ
Burton
A J
AJ
Dewberry
R M
RM
Gunn
J
J
Stephens-Lloyd
A
A
Cumberland
D C
DC
Gershlick
A
A
Crossman
D C
DC
D000483:Alleles; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D003327:Coronary Disease / Q000235:genetics* / Q000628:therapy; D006720:Homozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012008:Recurrence; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins