Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome

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

doi:10.1160/TH04-11-0735

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(05): 949-954
DOI: 10.1160/TH04-11-0735

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome

A possible implication of fractalkine in inflammatory activation

Authors

Alexander Niessner^*

¹Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Austria
Rodrig Marculescu^*

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

¹Department of Internal Medicine II, Division of Cardiology, 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, Medical University of Vienna, Austria
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, Medical University of Vienna, Austria
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

Abstract

Summary

Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 poly-morphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high-sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD. 720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9– and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not“balanced” by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk.

Keywords

Chemokine - fractalkine - polymorphism - acute coronary syndrome - C-reactive protein

Full Text

References

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