Host genetic basis for hepatitis C virus clearance: a role for blood collection centers.
Host genetic basis for hepatitis C virus clearance: a role for blood collection centers.
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DOI：
10.1097/moh.0b013e32833e7544
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发表时间：
2010-11
影响因子：
3.2
通讯作者：
Busch MP
中科院分区：
文献类型：
--
作者：
Selvarajah S;Tobler LH;Simmons G;Busch MP
影响HCV传播结果的宿主遗传因素尚未完全确定。然而，在感染相同亲本HCV毒株的个体之间观察到的自发清除率的巨大差异强烈表明遗传决定因素在宿主对HCV的免疫应答中的作用。这篇综述讨论了遗传关联研究，特别是那些在过去的一年中发表的，显示基因与自发和治疗诱导的HCV清除的联系。采血中心可以发挥重要作用，在增加样本量的HCV确认血清阳性捐助者解决与持续感染的大规模遗传关联研究的突出。最近突破性的全基因组关联研究（GWAS）和独立小组的靶向单核苷酸多态性（SNP）分析已经证明了免疫反应基因多态性，特别是白细胞介素（IL）-28B基因，与HCV清除密切相关。IL-28 B基因编码干扰素λ 3，一种先天免疫应答细胞因子。IL-28 B启动子区的SNP首先被证明与HCV治疗诱导的病毒清除相关，随后成为感染个体中HCV自发消退的关键决定因素。来自已解决和慢性HCV感染的献血者的样本有助于这些发现。这些遗传学研究提供了迄今为止最有力的证据，证明宿主遗传决定因素与HCV清除有关。这种大规模的遗传关联研究将促进更好地了解HCV疾病的发病机制，并有助于在未来的HCV有效的预后。鼓励血液中心继续并最好扩大参与本研究。
Host genetic factors influencing HCV transmission outcomes are incompletely defined. However, vast differences observed in rates of spontaneous clearance between individuals infected with the same parental HCV strain strongly indicate a role for genetic determinants in the host immune response to HCV. This review discusses genetic association studies, particularly those published in the past year, that show gene linkages with spontaneous and treatment-induced HCV clearance. The valuable role that blood collection centers can play in increasing the sample size of HCV confirmed seropositive donors with resolved versus persistent infections for large-scale genetic association studies is highlighted. Recent groundbreaking genome-wide association study (GWAS) and targeted single-nucleotide polymorphism (SNP) analysis from independent groups have demonstrated immune response gene polymorphisms, and particularly in the interleukin (IL)-28B gene, that are strongly linked to HCV clearance. The IL-28B gene encodes interferon lambda 3, an innate immune response cytokine. SNPs in the promoter region of IL-28B were first shown to be associated with HCV treatment-induced viral clearance and subsequently to be a key determinant of spontaneous HCV resolution in infected individuals. Samples from blood donors with resolved and chronic HCV infections have contributed to these findings. These genetic studies have provided the strongest evidence so far of a host genetic determinant linked to HCV clearance. Such large-scale genetic association studies will promote better understanding of HCV disease pathogenesis and assist in effective prognosis of HCV in the future. Continued and preferably expanded participation of blood centers in this research is encouraged.