| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
A Polymorphism in MAPKAPK3 Affects Response to Interferon Therapy for Chronic Hepatitis C |
|
言語 |
en |
| 作成者 |
Tsukada, Hironobu
Ochi, Hidenori
Maekawa, Toshiro
Abe, Hiromi
Fujimoto, Yoshifumi
Tsuge, Masataka
Takahash, Hiroshi
Kumada, Hiromitsu
Kamatani, Naoyuki
Nakamura, Yusuke
Chayama, Kazuaki
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
Copyright (c) 2009 AGA Institute Published by Elsevier Inc. |
| 内容記述 |
|
|
内容記述 |
Background & Aims: This study aimed to identify host single nucleotide polymorphisms (SNPs) that are associated with the efficacy of interferon (IFN) therapy in patients with chronic hepatitis C. Methods: We examined whether 116 tagging-SNPs from 13 genes that are involved in type I IFN signaling associate with the outcome of IFN therapy in Japanese case-control groups; the study included 468 sustained responders and 587 nonresponders. Results: We identified 2 SNPs (rs3792323 [A/T] and rs616589 [G/A]), located in intron 2 of mitogen-activated protein kinase-activated protein kinase 3 (MAPKAIPK3) that were associated with the outcome of IFN therapy in patients infected with hepatitis C virus (HCV) genotype 1b (P = 4.6 X 10(-5) and 4.8 X 10(-5), respectively). The 2 SNPs were in strong linkage disequilibrium and multivariate logistic regression analysis showed that rs3792323 is an independent factor associated with the IFN efficacy (genotype 1b; P =.0011). MAPKAPK3 is a kinase involved in the mitogen and stress responses, but the biological significance of MAPKAPK3 in IFN responses is poorly understood. By using an allele-specific transcript quantification assay in liver biopsy, we showed that allelespecific expression of MAPKAPK3 messenger RNA, corresponding to the risk allele for nonresponse, was significantly higher than that of the other allele. Luciferase reporter assay data indicated that overexpression of MAPKAPK3 inhibits IFN-alfa-induced gene transcription via IFN-stimulated response element and IFN gamma-activated site. Conclusions: The SNP rs3792323 in MAPKAPK3 associates with the outcome of IFN therapy in patients with HCV genotype 1b. Our functional analyses indicate that MAPKAPK3 inhibits IFN-alfa-induced antiviral activity. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
W B Saunders Co-Elesvier Inc |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AO |
|
出版タイプResource |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1053/j.gastro.2009.01.061 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
http://dx.doi.org/10.1053/j.gastro.2009.01.061 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0016-5085 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA0065394X |
| 開始ページ |
|
|
開始ページ |
1796 |
| 書誌情報 |
Gastroenterology
Gastroenterology
巻 136,
号 5,
p. 1796-1805,
発行日 2009
|
| 旧ID |
27695 |
Gastroenterology_136_1796.pdf (235.5 KB)
