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Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty
S E Francis1, N J Camp, A J Burton
1Cardiovascular Medicine Group, Division of Clinical Sciences, Clinical Sciences Centre, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, UK.
Insights
Genetic variations in the interleukin-1 receptor antagonist gene (IL-1RN*2) may protect against restenosis after percutaneous transluminal coronary angioplasty (PTCA), particularly in single-vessel disease patients.
Area of Science:
- Cardiovascular Genetics
- Inflammation Research
- Interventional Cardiology
Background:
- Percutaneous transluminal coronary angioplasty (PTCA) is frequently limited by restenosis, a re-narrowing of the coronary artery.
- Genetic factors are suspected to influence individual susceptibility to restenosis after PTCA.
- Understanding these genetic predispositions is crucial for improving PTCA outcomes.
Purpose of the Study:
- To investigate if restenosis after PTCA is an acute inflammatory process.
- To determine if specific gene polymorphisms, particularly within the interleukin-1 (IL-1) gene family, are associated with restenosis susceptibility.
- To explore the role of genetic predisposition in the blood vessel's response to injury.
Main Methods:
- Collected DNA from 171 patients undergoing elective PTCA.
- Genotyped four DNA polymorphisms in IL-1 related loci using polymerase chain reaction.
- Analyzed patient data based on restenosis status (defined by >50% luminal narrowing) at follow-up angiography.
Main Results:
- The IL-1RN*2 allele was significantly more common in patients who did not experience restenosis.
- IL-1RN*2 homozygosity was increased in non-restenosis patients, especially those with single-vessel disease.
- No significant associations were found for other IL-1 polymorphisms with restenosis.
Conclusions:
- The IL-1RN*2 polymorphism may offer protection against restenosis following PTCA in single-vessel disease patients.
- This finding suggests that an individual's inflammatory profile, influenced by genetics, can modulate arterial response to injury.
- Further research into inflammatory gene polymorphisms could lead to personalized PTCA strategies.
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.
Design:
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.