Pearlman Brian L
Center for Hepatitis C, Atlanta Medical Center, Atlanta, GA 30312, USA.
Curr Gastroenterol Rep. 2011 Feb;13(1):78-86. doi: 10.1007/s11894-010-0161-9.
The hypothesis that host genetics play an essential role in the ability not only to clear acute hepatitis C infection but also to achieve sustained virologic response (SVR) to interferon (IFN)-based therapy has been proved with the recent discovery of two single-nucleotide polymorphisms on chromosome 19. Variants in the minor allele rs8099917 and the proximate polymorphism rs12979860, 3 kb upstream of the interleukin (IL)-28B gene, which encodes the endogenous antiviral cytokine IFN-λ, are associated with SVR and with natural viral clearance. The disparate frequencies of these alleles in ethnic groups worldwide may well explain differing rates of SVR among them. The test for one of these polymorphisms is now commercially available and can serve as a powerful predictor of a patient's chance of achieving SVR. Perhaps more importantly, the test can help the clinician personally tailor the duration and even the type of therapy that is most appropriate for an individual patient, newly or chronically infected with the hepatitis C virus.
宿主遗传学不仅在清除急性丙型肝炎感染的能力中起着至关重要的作用，而且在基于干扰素（IFN）治疗实现持续病毒学应答（SVR）方面也起着至关重要的作用，这一假说已随着近期在19号染色体上发现两个单核苷酸多态性而得到证实。白细胞介素（IL）-28B基因上游3 kb处的次要等位基因rs8099917及其附近的多态性rs12979860的变体与SVR以及自然病毒清除相关，IL-28B基因编码内源性抗病毒细胞因子IFN-λ。这些等位基因在全球不同种族中的频率差异很可能解释了不同种族间SVR率的差异。现在，针对其中一种多态性的检测已商业化，可作为预测患者实现SVR几率的有力指标。也许更重要的是，该检测有助于临床医生针对新感染或慢性感染丙型肝炎病毒的个体患者，量身定制最适合该患者的治疗持续时间甚至治疗类型。
