Oxford University Clinical Research Unit-Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.
PLoS One. 2012;7(3):e33180. doi: 10.1371/journal.pone.0033180. Epub 2012 Mar 15.
The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380).
PubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven.
The fundamental question "Is susceptibility to severe influenza in humans heritable?" remains unanswered. Not because of a lack of genotyping or analytic tools, nor because of insufficient severe influenza cases, but because of the absence of a coordinated effort to define and assemble cohorts of cases. The recent pandemic and the ongoing epizootic of H5N1 both represent rapidly closing windows of opportunity to increase understanding of the pathogenesis of severe influenza through multi-national host genetic studies.
世界卫生组织已将宿主遗传学对严重流感易感性的研究确定为优先事项。进行了系统评价，以总结宿主遗传学在流感易感性中的作用的现有证据状况（PROSPERO 注册号：CRD42011001380）。
使用预先确定的策略在搜索日期之前搜索了 PubMed、Web of Science、Cochrane 图书馆和 OpenSIGLE 中的所有条目。两名审查员独立筛选了 1371 篇独特文章的标题和摘要，并选择了 72 篇全文出版物进行纳入。小鼠模型清楚地表明，宿主遗传学在对一系列人类和禽流感病毒的易感性中起着关键作用。编码干扰素诱导蛋白的 Mx 基因是研究最充分的，但它们与人类易感性的相关性尚不清楚。尽管 MxA 基因应被视为人类进一步研究的候选基因，但已提出了 100 多个其他候选基因。但是，没有数据将这些候选基因中的任何一个与人类的易感性相关联，唯一发表的人类研究的效力不足。一项谱系研究提出了流感相关死亡风险的可遗传性的中等证据，而 H5N1 病例的明显家族聚集表明宿主遗传因素，但这尚未得到证实。
“人类严重流感的易感性是否可遗传？”这一基本问题仍未得到解答。这不是由于缺乏基因分型或分析工具，也不是由于严重流感病例不足，而是由于缺乏协调一致的努力来定义和汇集病例队列。最近的大流行和 H5N1 的持续爆发都代表着通过跨国宿主遗传研究增加对严重流感发病机制的理解的机会窗口迅速关闭。
