Genetische Assoziationsstudien der immunologisch relevanten Gene CCR5, CX3CR1 und RANTES zur klinischen Risikostratifizierung von Patienten mit chronischer Hepatitis C

Hepatitis C represents an inflammtion of the liver, which is influenced by a variety of epidemological and viral factors, as well as genetical traits of the host. This study examined the influence and impact of genetical variations of chemokine receptors such as CCR 5 and CX3CR1 and the chemokine RANTES on chronic hepatitis C. The polymorphisms of the CC-chemokinereceptors delta32 (CCR5 delta32), the combined SNPs CX3CR1 V249I and T280M, as well as analysis of the haplotype of the RANTES gene were evaluated and correlated with chemical and histological parameters to reveal a potential influence on an antiviral therapy for chronic hepatitis C. A total of 330 patients suffering from chronic hepatitis C of two independent groups from the university hospital Aachen and Berlin and a control group, consisiting of 152 age- and gender-matched hepatitis C virus negative individuals with a similar risk of exposition, were included in this study. The results of this study revealed that:(1) None of the tested SNPs was associated with an increased susceptibility towards an infection with hepatitis C. Analysis of the haplotypes of the RANTES gene also showed no difference between the study and control groups. (2) Analysis of the CCR5 delta32-deletion polymorphisms showed no significant difference between HCV-RNA viral load, liver enzyme profile or fibrosis score in regard to presence or absence of the polymorphe CCR5 delta32-alleles. A higher level of inflammation was found in the liver biopsies of the patient group of the University Hospital Aachen and a reduced response to the medical therapy of the patients of the Berlin group in the presence of the CCR5 delta32-mutation. However, these findings could not be confirmed by studying the other patient group of Aachen or Berlin, respectively, neither when analyzing the two combined groups of patients.(3) The CX3CR1 249I-allel was found to be associated with a higher HCV-RNA viral load and a higher degree of fibrosis of the liver biopsies. This finding was confirmed in the combined analysis of the SNPs CX3CR1 V249I and T280M.(4) Analysis of the RANTES gene identified four frequent haplotypes. RANTES-haplotypes, which carry the RANTES Int 1.1 C and the 3' 222 C- allel were found in a significantly higher number among patients with a negative response to therapy. This finding was also confirmed for patients with the HCV-genotype 1+4. These results suggest that the RANTES-haplotypes might contribute to the complex interaction between the hepatitis C virus and the polygenic determined immune response of the patient receiving antiviral therapy. The results of this study underline the importance and influence of chemokines and their receptors on the progress of hepatitis C and will help to develop new therapeutic strategies against this devastating illness. However, further investigation including a larger number of individuals, as well as different study populations is necessary to confirm the findings of this study.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Werth, Alexa

Contributors dc:contributor

• Rossaint, Rolf

• info:eu-repo/classification/ddc/610
• Hepatitis C
• RANTES
• CCR5-Rezeptor
• Haplotyp
• RFLP
• Polymerase-Kettenreaktion
• Medizin
• Risikostratifizierung
• haplotype
• risk stratification

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112795%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50242