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ID 30405
file
creator
Maekawa, Toshiro
Hayes, C. Nelson
Miki, Daiki
Mitsui, Fukiko
Takahashi, Shouichi
Ohishi, Waka
Kubo, Michiaki
Nakamura, Yusuke
subject
IL28
SNP
histological activity
inflammation
gamma GTP
NDC
Medical sciences
abstract
Background & Aims: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus.

Methods: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n = 364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings.

Results: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p = 1.21 × 10-4 and 0.034) and levels of gamma-GTP significantly lower (p = 0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p = 0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p = 0.001, 0.0003, 0.0013, and 0.0348, respectively).

Conclusions: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases.
journal title
Journal of Hepatology
volume
Volume 53
issue
Issue 3
start page
439
end page
443
date of issued
2010-09
publisher
Elsevier Science BV
issn
0168-8278
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2010 European Association for the Study of the Liver Published by Elsevier Ireland Ltd.
relation url
department
Graduate School of Biomedical Science



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