Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients.
OBJECTIVE
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 x 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.
Abe
Hiromi
H
Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.
Ochi
Hidenori
H
Maekawa
Toshiro
T
Hayes
C Nelson
CN
Tsuge
Masataka
M
Miki
Daiki
D
Mitsui
Fukiko
F
Hiraga
Nobuhiko
N
Imamura
Michio
M
Takahashi
Shoichi
S
Ohishi
Waka
W
Arihiro
Koji
K
Kubo
Michiaki
M
Nakamura
Yusuke
Y
Chayama
Kazuaki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014758:Viral Core Proteins / Q000235:genetics; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood; D000095022:Interferon Lambda
D017931:DNA Primers; D007372:Interferons; D007378:Interleukins; D014758:Viral Core Proteins; D005723:gamma-Glutamyltransferase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda