Interleukin-1 cluster combined genotype and restenosis after balloon angioplasty.
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 (> or = 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.
Marculescu
Rodrig
R
Department of Internal Medicine II, Division of Angiology, University of Vienna, Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. martin.schillinger@akh-wien.ac.at
Mlekusch
Wolfgang
W
Exner
Markus
M
Sabeti
Schila
S
Michor
Stefanie
S
Rumpold
Helmut
H
Mannhalter
Christine
C
Minar
Erich
E
Wagner
Oswald
O
Schillinger
Martin
M
D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001161:Arteriosclerosis / Q000235:genetics; D023903:Coronary Restenosis / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D005810:Multigene Family; D009154:Mutation; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins