Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension

Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphism...

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Main Authors: Bianca Marasini, Roberta Cossutta, Carlo Selmi, Maria Rosa Pozzi, Marco Gardinali, Marco Massarotti, Maddalena Erario, Lodovica Battaglioli, Maria Luisa Biondi
Format: Article
Language:English
Published: Wiley 2005-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1080/17402520500303297
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author Bianca Marasini
Roberta Cossutta
Carlo Selmi
Maria Rosa Pozzi
Marco Gardinali
Marco Massarotti
Maddalena Erario
Lodovica Battaglioli
Maria Luisa Biondi
author_facet Bianca Marasini
Roberta Cossutta
Carlo Selmi
Maria Rosa Pozzi
Marco Gardinali
Marco Massarotti
Maddalena Erario
Lodovica Battaglioli
Maria Luisa Biondi
author_sort Bianca Marasini
collection DOAJ
description Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.
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spelling doaj-art-1a29effcbb4a484f9c4314fde0d890b32025-08-20T03:54:21ZengWileyClinical and Developmental Immunology1740-25221740-25302005-01-0112427527910.1080/17402520500303297Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial HypertensionBianca Marasini0Roberta Cossutta1Carlo Selmi2Maria Rosa Pozzi3Marco Gardinali4Marco Massarotti5Maddalena Erario6Lodovica Battaglioli7Maria Luisa Biondi8Rheumatology Unit, Department of Medicine, Surgery and Dentistry, Humanitas Clinical Institute, University of Milan, Rozzano, Milan, ItalyRheumatology Unit, Department of Medicine, Surgery and Dentistry, Humanitas Clinical Institute, University of Milan, Rozzano, Milan, ItalyDivision of Internal Medicine, San Paolo School of Medicine, University of Milan, ItalyDepartment of Medicine, S. Gerardo Hospital, Monza, ItalyDepartment of Medicine, S. Gerardo Hospital, Monza, ItalyDepartment of Medicine, S. Gerardo Hospital, Monza, ItalyClinical Chemistry Laboratory, S. Paolo Hospital, Milan, ItalyClinical Chemistry Laboratory, S. Paolo Hospital, Milan, ItalyClinical Chemistry Laboratory, S. Paolo Hospital, Milan, ItalyFractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.http://dx.doi.org/10.1080/17402520500303297
spellingShingle Bianca Marasini
Roberta Cossutta
Carlo Selmi
Maria Rosa Pozzi
Marco Gardinali
Marco Massarotti
Maddalena Erario
Lodovica Battaglioli
Maria Luisa Biondi
Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
Clinical and Developmental Immunology
title Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
title_full Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
title_fullStr Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
title_full_unstemmed Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
title_short Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension
title_sort polymorphism of the fractalkine receptor cx3cr1 and systemic sclerosis associated pulmonary arterial hypertension
url http://dx.doi.org/10.1080/17402520500303297
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