title: Fractalkine receptor polymorphisms V2491 and T280M as genetic risk factors for restenosis.
abstract: 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 V2491 and T280M. Restenosis occurred in 25% of patients, and recurrent (> 1) restenosis at the target lesion in 8%. The allele 1249 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 1249 lacking the allele M280 were at an elevated risk of restenosis (P = 0.006) and, accordingly, the haplotype containing 1249 but not M280 was more frequent in patients with restenosis (P = 0.001). In conclusion, the CX3CR1 1249 allele is associated with an increased risk of restenosis while the CX3CR1 M280 allele might counteract the harmful influence of 1249. 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.
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. alexander.niessner@meduniwien.ac.at
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.forename: Heda
authors.initials: H
authors.lastname: Kvakan
authors.forename: Arvand
authors.initials: A
authors.lastname: Haschemi
authors.forename: Georg
authors.initials: G
authors.lastname: Endler
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Weyand
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
mesh_terms: D000483:Alleles; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000073883:CX3C Chemokine Receptor 1; D023903:Coronary Restenosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000235:genetics*; D015728:Receptors, HIV / Q000235:genetics*; D012307:Risk Factors
chemical_list: D000073883:CX3C Chemokine Receptor 1; D018121:Receptors, Cytokine; D015728:Receptors, HIV