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Thromb Haemost 2003; 90(03): 491-500
DOI: 10.1160/TH03-01-0064
Wound Healing and Inflammation/Infection
Schattauer GmbH

Interleukin-1 cluster combined genotype and restenosis after balloon angioplasty

Rodrig Marculescu
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Wolfgang Mlekusch
2   Departments of Angiology, University of Vienna, Medical School, Austria
,
Markus Exner
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Schila Sabeti
2   Departments of Angiology, University of Vienna, Medical School, Austria
,
Stefanie Michor
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Helmut Rumpold
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Christine Mannhalter
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Erich Minar
2   Departments of Angiology, University of Vienna, Medical School, Austria
,
Oswald Wagner
1   Departments of Medical and Chemical laboratory Diagnostics, University of Vienna, Medical School, Austria
,
Martin Schillinger
2   Departments of Angiology, University of Vienna, Medical School, Austria
› Author Affiliations
Financial support: The study was supported by grant P15231 of the “Fonds zur Förderung der Wissenschaftlichen Forschung” (to M.E. and M.S.).
Further Information

Publication History

Received 31 January 2003

Accepted after revision 18 May 2003

Publication Date:
05 December 2017 (online)

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Summary

The interleukin-1 system is fundamentally involved in the pathogenesis of restenosis after percutaneous transluminal angioplasty (PTA). In order to further define the clinical impact of genetic variation in this potent proinflammatory pathway we investigated the joint effects of two single nucleotide polymorphisms in the interleukin-1 beta gene [IL-1B(–511) and IL-1B(+3954)] and a variable number tandem repeat polymorphism in intron 2 of the interleukin 1 receptor antagonist gene (IL-1RN VNTR) on postintervention inflammation and occurrence of restenosis in 183 consecutive patients who underwent successful femoropopliteal PTA. C-reactive protein (CRP) and serum amyloid A (SAA) were determined pre- and 48 hours postintervention. Patients were followed up to 12 months for the occurrence of postangioplasty restenosis (≥50 %). When analyzed separately, none of the polymorphisms was associated either with inflammation or restenosis. However, when the IL-1B (–511) and the IL-1RN VNTR genotypes were combined, a highly significant relationship was observed: Non-carriers of the two repeat allele of the IL-1RN VNTR (IL-1RN*2) who were heterozygous and homozygous for the IL-1B (–511)T allele exhibited a gradually increased inflammatory response and a higher restenosis risk. In contrast, carriers of the IL-1RN*2 and the IL-1B (–511)T allele showed a significantly better outcome.

This remarkable gene dose-dependent association emphasizes the advantage of considering combinations of genetic markers rather that isolated polymorphisms in the analysis of multifactorial vascular disease.

Keywords

Atherosclerosis - restenosis - cytokines - gene mutations