Hepatic expression levels of interferons and interferon-stimulated genes in patients with chronic hepatitis C: A phenotype-genotype correlation study.
Hepatic expression levels of interferons and interferon-stimulated genes in patients with chronic hepatitis C: A phenotype-genotype correlation study.
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DOI：
10.1038/gene.2015.11
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发表时间：
2015-07
影响因子：
5
通讯作者：
Liang TJ
中科院分区：
文献类型：
--
作者：
Noureddin M;Rotman Y;Zhang F;Park H;Rehermann B;Thomas E;Liang TJ
IFNL 4与丙型肝炎病毒治疗反应和III型干扰素（IFN）有关。我们研究了干扰素和干扰素刺激基因（ISGs）的肝脏表达与聚乙二醇干扰素和利巴韦林治疗反应之间的功能相关性。采用qPCR方法检测65例慢性丙型肝炎（CHC）患者肝组织中I型IFN（IFNA 1、IFNB 1）、II型IFN（IFNG）、III型IFN（IFNL 1、IFNL 2/3）、IFNL 4和ISG的表达，并分析其与IFNL 4相关的rs368234815和IFNL 3相关的rs 12989760基因型。I型和III型IFN内以及III型IFN和IFNL 4之间的肝脏表达存在强相关性，但其他IFN类型之间无相关性。ISGs的表达与III型IFN和IFNL 4相关，但与I型IFN无关。与非CC患者相比，IFNL 3 rs 12979860 CC患者的ISG和IFNL 2/3 mRNA水平较低，与无应答者相比，治疗应答者的ISG和IFNL 2/3 mRNA水平较低。IFNL 4-ΔG基因型与高ISG水平和无应答相关。CHC中ISG的肝脏水平与IFNL 2/3和IFNL 4表达相关，表明IFNLs而不是其他类型的IFN驱动ISG表达。肝脏IFNL 2/3表达在功能上与IFNL 4和IFNL 3多态性相关，这可能解释了ISG表达与治疗反应之间的紧密关联。
IFNL4 is linked to hepatitis C virus treatment response and type III interferons (IFNs). We studied the functional associations among hepatic expressions of IFNs and IFN-stimulated genes (ISGs), and treatment response to peginterferon and ribavirin. Type I IFNs (IFNA1, IFNB1), type II (IFNG), type III (IFNL1, IFNL2/3), IFNL4 and ISG hepatic expressions were measured by qPCR from in 65 chronic hepatitis C (CHC) patients whose IFNL4-associated rs368234815 and IFNL3-associated rs12989760 genotype were determined. There was a robust correlation of hepatic expression within type I and type III IFNs and between type III IFNs and IFNL4 but no correlation between other IFN types. Expression of ISGs correlated with type III IFNs and IFNL4 but not with type I IFNs. Levels of ISGs and IFNL2/3 mRNAs were lower in IFNL3 rs12979860 CC patients compared with non-CC patients, and in treatment responders, compared with nonresponders. IFNL4-ΔG genotype was associated with high ISG levels and nonresponse. Hepatic levels of ISGs in CHC are associated with IFNL2/3 and IFNL4 expression, suggesting that IFNLs, not other types of IFNs, drive ISG expression. Hepatic IFNL2/3 expression is functionally linked to IFNL4 and IFNL3 polymorphisms, potentially explaining the tight association among ISG expression and treatment response.
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影响因子：
2.5
作者：
Fujiwara, D;Hino, K;Okita, K
通讯作者：
Okita, K
影响因子：
30.5
作者：
McFarland, Addle P.;Horner, Stacy M.;Jarret, Abigail;Joslyn, Rochelle C.;Bindewald, Eckart;Shapiro, Bruce A.;Delker, Don A.;Hagedorn, Curt H.;Carrington, Mary;Gale, Michael, Jr.;Savan, Ram
通讯作者：
Savan, Ram
影响因子：
29.4
作者：
Randall, Glenn;Chen, Limin;McGilvray, Ian D.
通讯作者：
McGilvray, Ian D.
DOI：
10.1056/nejmra1213651
发表时间：
2013-05-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liang TJ;Ghany MG
通讯作者：
Ghany MG
DOI：
10.1084/jem.20131557
发表时间：
2014-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Duong FH;Trincucci G;Boldanova T;Calabrese D;Campana B;Krol I;Durand SC;Heydmann L;Zeisel MB;Baumert TF;Heim MH
通讯作者：
Heim MH