Waldron Paul Ravi, Belitskaya-Lévy Ilana, Chary Aarthi, Won Johann, Winters Mark, Monto Alexander, Ryan James, Lazzeroni Laura C, Holodniy Mark
VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Division of Infectious Diseases & Geographic Medicine, Stanford University, Stanford, CA 94305, USA.
Cooperative Studies Program Coordinating Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
J Immunol Res. 2016;2016:6530436. doi: 10.1155/2016/6530436. Epub 2016 Jun 2.
Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection.
背景。全球数以百万计的人感染了丙型肝炎病毒（HCV），其中30%会自发清除感染。未经抗病毒治疗而实现HCV清除的原因尚不清楚。方法。采集慢性HCV感染患者或有自发清除证据患者的血液用于DNA分析。为克服预期的小样本量限制，初步分析包括对12个基于与宿主对HCV感染免疫反应已知关联而预先选择的基因进行候选基因分析。为进一步降低多重检验对效能的影响，使用Illumina Quad 610/660W芯片上检测的所有相关单核苷酸多态性（SNP）对每个基因进行单似然比检验。在所有分析中采用逐步置换法调整多重检验。结果。分别纳入95例HCV慢性感染患者和62例有自发清除的患者进行分析。HLA - DQB1基因（p = 1.76×10⁻⁵）和IL - 6基因（p = 0.0007）与HCV自发清除显著相关。IL - 28B与自发清除无显著关联（p = 0.17）。结论。我们的全基因分析策略确定了IL - 6与HCV感染自发清除之间先前未报道的关联。我们还证实了HLA - DQB1与HCV感染自发缓解相关的发现。
