CCR5, RANTES and CX3CR1 polymorphisms: possible genetic links with acute heart rejection

Détails

ID Serval
serval:BIB_1F0D1463AFB5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CCR5, RANTES and CX3CR1 polymorphisms: possible genetic links with acute heart rejection
Périodique
Transplantation
Auteur(s)
Simeoni  E., Vassalli  G., Seydoux  C., Ramsay  D., Noll  G., von Segesser  L. K., Fleury  S.
ISSN
0041-1337 (Print)
Statut éditorial
Publié
Date de publication
11/2005
Volume
80
Numéro
9
Pages
1309-15
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 15
Résumé
BACKGROUND: The inflammation response is modulated by the elaborated chemokine-chemokine receptor system, which also plays an important role in the development of acute rejection (AR). In this study, we hypothesized that functional genetic variants of some of these modulatory proteins might influence the outcome of AR. METHODS: In a retrospective analysis of a cohort of heart transplanted patients (n=158), we examined eight polymorphisms in four genes implicated in this inflammatory process: RANTES, CCR5, CCR2 and CX3CR1. On the basis of timing occurrence, AR episodes (grade>or= 3A) were classified in "early" (0-3 months posttransplantation; EAR) or "late" outcomes (4-12 months posttransplantation; LAR). RESULTS: The incidences of EAR and LAR were 57.6% and 41%, respectively. Number of LAR episodes was significantly higher in subjects that have already experienced one or more EAR episodes, as compared to subjects that had no EAR (median [25%-75%]: 4 () vs. 1 [1-2.5] respectively; P<0.0001). Statistical univariate analysis showed that none of the mentioned polymorphisms were correlated with EAR or LAR. However, allele-allele association analysis showed that subjects carrying both the CX3CR1 249I allele and CCR5 No-E haplotypes were significantly at lower risk of experiencing EAR (OR=0.2 [95%-CI=0.1-0.5], P=0.001). In contrast subjects carrying both the CCR5 E haplotype and the RANTES -403A allele were significantly at higher risk to develop LAR (OR=8.1 [95%-CI=2.3-28.7], P=0.002). CONCLUSIONS: This exploratory study in heart transplantation suggests that the outcomes of EAR and LAR episodes may be influenced by genetic variant interactions such as "CX3CR1 249I*CCR5 No-E" and "CCR5 E*RANTES -403A."
Mots-clé
Acute Disease Alleles Cohort Studies Graft Rejection/*genetics Haplotypes Heart Transplantation/*immunology Humans Membrane Proteins/*genetics Polymorphism, Genetic RANTES/*genetics Receptors, CCR5/*genetics Receptors, Chemokine/*genetics Retrospective Studies
Pubmed
Web of science
Création de la notice
28/01/2008 10:11
Dernière modification de la notice
20/08/2019 12:55
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