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Nature:基因差异影响丙肝治疗效果

来源:新华网 2009-08-17 16:47

专题:Nature报道

不同丙肝患者接受相同治疗,效果却大不一样,有些患者甚至会出现严重不良反应。美国一项新研究发现,这与人体中某个基因的微小变化密切相关。

美国杜克大学的戴维·戈尔茨坦等人8月16日在《自然》杂志网络版上发表论文说,人体DNA(脱氧核糖核酸)分子中有一个与防感染基因IL28B相连的基因,当这一基因的碱基T被碱基C替换时,人们接受丙肝疗法的效果便会发生显著变化。

戈尔茨坦等人研究了1600多名丙肝患者后发现,碱基T被碱基C替换后,这个基因便变成了“好基因”,因为出现这种变化的丙肝患者比没有变化的患者的治疗效果要好得多。具有“好基因”的丙肝患者80%都被治愈,而没有“好基因”的丙肝患者只有30%被治愈。

戈尔茨坦在一份声明中说,这是一项很有价值的发现,它可以解释为什么有些丙肝患者的治疗效果很好,有些人却治疗无效。将来丙肝患者可根据他们的基因来选择适当的治疗方法。

据统计,全球有1.7亿人感染丙肝,目前治疗这种疾病最有效的药物是干扰素加上利巴韦林,但不同人之间效果大不相同,科学家此前一直不知道原因所在。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature advance online publication 16 August 2009 | doi:10.1038/nature08309

Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance

Dongliang Ge1, Jacques Fellay1, Alexander J. Thompson2, Jason S. Simon3, Kevin V. Shianna1, Thomas J. Urban1, Erin L. Heinzen1, Ping Qiu3, Arthur H. Bertelsen3, Andrew J. Muir2, Mark Sulkowski4, John G. McHutchison2 & David B. Goldstein1

1 Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, North Carolina 27708, USA
2 Duke Clinical Research Institute and Division of Gastroenterology, School of Medicine, Duke University, Durham, North Carolina 27705, USA
3 Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA
4 Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America1. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-α-2b (PegIFN-α-2b) or -α-2a (PegIFN-α-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African ancestry. In addition to limited efficacy, treatment is often poorly tolerated because of side effects that prevent some patients from completing therapy. For these reasons, identification of the determinants of response to treatment is a high priority. Here we report that a genetic polymorphism near the IL28B gene, encoding interferon-λ-3 (IFN-λ-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry (P = 1.06  10-25) and African-Americans (P = 2.06  10-3). Because the genotype leading to better response is in substantially greater frequency in European than African populations, this genetic polymorphism also explains approximately half of the difference in response rates between African-Americans and patients of European ancestry.

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