Fractalkine receptor polymorphisms V249I and T280M as genetic risk factors for restenosis

Alexander Niessner; Rodrig Marculescu; Heda Kvakan; Arvand Haschemi; Georg Endler; Cornelia M. Weyand; Gerald Maurer; Christine Mannhalter; Johann Wojta; Oswald Wagner; Kurt Huber

doi:10.1160/TH05-06-0417

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 94(06): 1251-1256
DOI: 10.1160/TH05-06-0417

Wound Healing and Inflammation/Infection

Schattauer GmbH

Fractalkine receptor polymorphisms V249I and T280M as genetic risk factors for restenosis

Alexander Niessner

¹Department of Internal Medicine II, Division of Cardiology

³Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA

,

Rodrig Marculescu

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria

,

Heda Kvakan

¹Department of Internal Medicine II, Division of Cardiology

,

Arvand Haschemi

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria

,

Georg Endler

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria

,

Cornelia M. Weyand

³Department of Medicine, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA

,

Gerald Maurer

¹Department of Internal Medicine II, Division of Cardiology

,

Christine Mannhalter

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria

,

Johann Wojta

¹Department of Internal Medicine II, Division of Cardiology

,

Oswald Wagner

²Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria

,

Kurt Huber

⁴3 rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminen-Hospital, Vienna, Austria

› Institutsangaben

Abstract

Summary

The chemokine fractalkine (FKN) recruits leukocytes into lesions of the arterial wall, which may lead to restenosis after stenting. FKN also regulates proliferation of smooth muscle cells, another mechanism pivotal to neointimal thickening. We assessed the hypothesis that functionally important polymorphisms of the FKN receptor CX3CR1 influence restenosis after coronary stenting. Three hundred and sixty-five patients undergoing coronary stenting were genotyped for the CX3CR1 polymorphisms V249I and T280M. Restenosis occurred in 25% of patients, and recurrent (> 1) restenosis at the target lesion in 8%.The allele I249 was associated with an increased risk of restenosis (adjusted odds ratio 2.4, 95% confidence interval: 1.3–4.2,P = 0.003) and recurrent restenosis (odds ratio 2.7,95% confidence interval:1.3–5.9,P = 0.011).Particularly, patients with I249 lacking the allele M280 were at an elevated risk of restenosis (P = 0.006) and, accordingly, the haplotype containing I249 but not M280 was more frequent in patients with restenosis (P = 0.001). In conclusion, the CX3CR1 I249 allele is associated with an increased risk of restenosis while the CX3CR1 M280 allele might counteract the harmful influence of I249.These findings show the importance of the chemokine FKN and genetic variations of its receptor for restenosis after coronary stenting. Recognition of these inherited risk modifiers may help to individualize treatment of coronary stenosis.

Keywords

Restenosis - stent - chemotaxis - fractalkine - single nucleotide - polymorphism

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Referenzen

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