Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 275-279 |
| Number of pages | 5 |
| Journal | Clinical and Developmental Immunology |
| Volume | 12 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Dec 2005 |
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Keywords
- Fractalkine
- Genetics
- Pulmonary hypertension
- Scleroderma
ASJC Scopus subject areas
- Immunology
- Cell Biology
- Developmental Biology
Cite this
Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension. / Marasini, Bianca; Cossutta, Roberta; Selmi, Carlo; Pozzi, Maria Rosa; Gardinali, Marco; Massarotti, Marco; Erario, Maddalena; Battaglioli, Lodovica; Biondi, Maria Luisa.
In: Clinical and Developmental Immunology, Vol. 12, No. 4, 12.2005, p. 275-279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension
AU - Marasini, Bianca
AU - Cossutta, Roberta
AU - Selmi, Carlo
AU - Pozzi, Maria Rosa
AU - Gardinali, Marco
AU - Massarotti, Marco
AU - Erario, Maddalena
AU - Battaglioli, Lodovica
AU - Biondi, Maria Luisa
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
KW - Fractalkine
KW - Genetics
KW - Pulmonary hypertension
KW - Scleroderma
UR - http://www.scopus.com/inward/record.url?scp=30344472950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30344472950&partnerID=8YFLogxK
U2 - 10.1080/17402520500303297
DO - 10.1080/17402520500303297
M3 - Article
C2 - 16584113
AN - SCOPUS:30344472950
VL - 12
SP - 275
EP - 279
JO - Clinical and Developmental Immunology
JF - Clinical and Developmental Immunology
SN - 1740-2522
IS - 4
ER -