全基因组关联研究自发性丙型肝炎病毒感染的解决：来自多个队列的数据。
Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
机构信息
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Ann Intern Med. 2013 Feb 19;158(4):235-45. doi: 10.7326/0003-4819-158-4-201302190-00003.
UNLABELLED
Chinese translation
BACKGROUND
Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood.
OBJECTIVE
To evaluate the host genetic basis for spontaneous resolution of HCV infection.
DESIGN
2-stage, genome-wide association study.
SETTING
13 international multicenter study sites.
PATIENTS
919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence).
MEASUREMENTS
Frequencies of 792 721 single nucleotide polymorphisms (SNPs).
RESULTS
Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 × 10-30) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 × 10-16) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015).
LIMITATION
Epigenetic effects were not studied.
CONCLUSION
IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection.
目的
评估丙型肝炎病毒 (HCV) 感染自发清除的宿主遗传基础。
设计
两阶段全基因组关联研究。
地点
13 个国际多中心研究地点。
患者
919 例血清 HCV 抗体阳性但无 HCV RNA（自发清除）和 1482 例血清 HCV 抗体和 HCV RNA 阳性（持续存在）。
测量
792721 个单核苷酸多态性 (SNP) 的频率。
结果
在第 19 号染色体 19q13.13 和第 6 号染色体 6p21.32 上发现了自发清除者和持续存在者之间等位基因频率的差异。在第 19 号染色体上，位于 IL-28B 附近的等位基因频率差异包括 rs12979860（每个等位基因的总体比值比，0.45；P=2.17×10-30）和跨越 55000 个碱基对的 10 个额外 SNP。在第 6 号染色体上，位于 HLA Ⅱ类基因附近的等位基因频率差异包括 rs4273729（每个等位基因的总体比值比，0.59；P=1.71×10-16），位于 DQB1*03:01 附近，还有另外 116 个跨越 1090000 个碱基对的 SNP。第 19 号和第 6 号染色体上的关联是独立和累加的，分别解释了欧洲和非洲血统人群 HCV 清除率变异的 14.9%（95%CI，8.5%至 22.6%）和 15.8%（CI，4.4%至 31.0%）。在另外 745 名患者中复制第 6 号染色体 SNP rs4272729 证实了这一发现（P=0.015）。
局限性
未研究表观遗传效应。
结论
IL-28B 和 HLA Ⅱ类与 HCV 感染的自发清除独立相关，标记 IL-28B 和 DQB1*03:01 的 SNP 可能解释了 HCV 感染自发清除的约 15%。
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