Abstract |
Transporter associated with antigen processing (TAP) and low molecular mass polypeptides (LMP) play crucial roles in the human leukocyte antigen (HLA) class I-restricted antigen presenting systems. This study was performed to elucidate whether these antigen-presenting gene polymorphisms could influence the response to interferon (IFN) treatment in patients with chronic hepatitis C. Polymorphisms of TAP and LMP genes in 175 hepatitis C virus (HCV) patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of these genes were compared between sustained-responders (n=49) and nonresponders (n=126), classified by biochemical and virological responses to IFN. The distributions of TAP1*, TAP2*, and LMP2 genes between sustained-responders and nonresponders did not differ. However, LMP7-K gene frequency in sustained-responders was higher than that in nonresponders [odds ratio 2.3 (95% confidence interval 1.1-4.6); 16%vs 7.9%]. Multivariate analysis revealed that LMP7-K and HCV- RNA quantity were independent factors influencing the outcome of IFN therapy [4.5 (1.4-14); P=0.011, 0.40 (0.24-0.65); P=0.0003, respectively]. Furthermore, among patients with a low viral load (< or = 2.0 Meq/mL), the LMP7-K positive patients had an even higher ratio of sustained response compared to those without LMP7-K [5.9 (1.6-22); 82%vs 44%; P=0.0062]. These findings suggest that a single nucleotide polymorphism of LMP7 gene is one of the important host factors which independently influence the response to IFN in patients with chronic hepatitis C.
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Authors | Y Sugimoto, N Kuzushita, T Takehara, T Kanto, T Tatsumi, T Miyagi, M Jinushi, K Ohkawa, M Horimoto, A Kasahara, M Hori, Y Sasaki, N Hayashi |
Journal | Journal of viral hepatitis
(J Viral Hepat)
Vol. 9
Issue 5
Pg. 377-84
(Sep 2002)
ISSN: 1352-0504 [Print] England |
PMID | 12225333
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 3
- ATP-Binding Cassette Transporters
- Integration Host Factors
- Interferon-alpha
- Multienzyme Complexes
- TAP2 protein, human
- Cysteine Endopeptidases
- LMP7 protein
- Proteasome Endopeptidase Complex
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 3
- ATP-Binding Cassette Transporters
(genetics)
- Adult
- Cysteine Endopeptidases
(genetics)
- Female
- Gene Frequency
- Genotype
- Hepatitis C, Chronic
(drug therapy, genetics, virology)
- Humans
- Integration Host Factors
- Interferon-alpha
(therapeutic use)
- Male
- Multienzyme Complexes
- Multivariate Analysis
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- Proteasome Endopeptidase Complex
- Treatment Outcome
- Viral Load
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