Document Detail


A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis.
MedLine Citation:
PMID:  20967855     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The UPAR gene encodes a pleiotropic receptor (urokinase-type plasminogen activator receptor [uPAR]) involved in fibrosis, immunity, angiogenesis, and vascular remodeling. Previous studies have implicated uPAR in systemic sclerosis (SSc) vasculopathy and impaired angiogenesis. We undertook this study to investigate whether UPAR gene promoter polymorphisms might be associated with SSc phenotypes in the European Caucasian population.
METHODS: We studied a total population of 1,339 individuals. The Italian discovery cohort comprised 388 SSc patients and 391 healthy controls. The French replication cohort consisted of 344 SSc patients and 216 healthy controls. The UPAR rs344781 and rs4251805 single-nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay.
RESULTS: In the Italian cohort, the rs344781 G allele was associated with SSc-related digital ulceration (odds ratio [OR] 1.39), pulmonary arterial hypertension (PAH) (OR 1.81), anticentromere antibody (ACA) positivity (OR 1.45), and limited cutaneous SSc (lcSSc) (OR 1.37). The rs344781 GG genotype was associated with SSc-related (OR 3.79), ACA-positive SSc (OR 2.17), and lcSSc (OR 1.96). Allelic and genotypic associations with SSc-related digital ulceration and ACA-positive SSc were replicated in the French sample. Combined analyses showed an association of the rs344781 G allele and GG genotype with SSc-related digital ulceration (allele OR 1.41, genotype OR 2.15), SSc-related PAH (allele OR 1.65, genotype OR 3.16), ACA-positive SSc (allele OR 1.47, genotype OR 2.40), and lcSSc (allele OR 1.34, genotype OR 1.77). In a multivariate logistic regression analysis model including the above associated phenotypes of SSc patients, the rs344781 GG genotype remained an independent risk factor for SSc-related digital ulceration (OR 1.96) and SSc-related PAH (OR 2.68).
CONCLUSION: The UPAR rs344781 gene variant is associated with the SSc vascular phenotype.
Authors:
Mirko Manetti; Yannick Allanore; Lucile Revillod; Cinzia Fatini; Serena Guiducci; Giovanna Cuomo; Claudia Bonino; Valeria Riccieri; Laura Bazzichi; Vasiliki Liakouli; Paola Cipriani; Roberto Giacomelli; Rosanna Abbate; Stefano Bombardieri; Guido Valesini; Carlomaurizio Montecucco; Gabriele Valentini; Lidia Ibba-Manneschi; Marco Matucci-Cerinic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  63     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-56     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 by the American College of Rheumatology.
Affiliation:
University of Florence and Excellence Centre for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, Florence, Italy. mirkomanetti@yahoo.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Chi-Square Distribution
Female
Genetic Association Studies
Genetic Variation
Genotype
Humans
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Receptors, Urokinase Plasminogen Activator / genetics*
Scleroderma, Systemic / complications,  genetics*
Vascular Diseases / complications,  genetics*
Chemical
Reg. No./Substance:
0/PLAUR protein, human; 0/Receptors, Urokinase Plasminogen Activator

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