Klebanov Nikolai
Dermatology, Massachusetts General Hospital, Boston, USA.
Cureus. 2018 Aug 27;10(8):e3210. doi: 10.7759/cureus.3210.
In contemporary medical practice, approaches to infectious disease management have been primarily rooted in a pathogen-centered model. However, host genetics also contribute significantly to infectious disease burden. The fast expansion of bioinformatics techniques and the popularization of the genome-wide association study (GWAS) in recent decades have allowed for rapid and affordable high-throughput genomic analyses. This review focuses on the host model of infectious disease with particular emphasis placed on the genetic variations underlying observed infectious disease predisposition. First, we introduce observational twin-twin concordance studies of diseases such as poliomyelitis, tuberculosis, and hepatitis which suggest the important role of host genetics. We review the well-established links between specific genetic alterations and predisposition to malaria ( and ), Creutzfeldt-Jacob disease (CJD), human immunodeficiency virus (HIV), and Norwalk virus. Finally, we discuss the novel findings yielded by modern GWAS studies, which suggest the strong contribution of immunologic variation in the major histocompatibility complex (MHC) to host genetic infectious disease susceptibility. Future large-scale genomic studies hold promise in providing insights into immunology-pathogen links and may allow for the development of personalized genomic approaches to infectious disease prevention and treatment.
在当代医学实践中，传染病管理方法主要基于以病原体为中心的模式。然而，宿主遗传学对传染病负担也有显著影响。近几十年来，生物信息学技术的快速发展和全基因组关联研究（GWAS）的普及使得快速且经济实惠的高通量基因组分析成为可能。本综述聚焦于传染病的宿主模型，特别强调观察到的传染病易感性背后的基因变异。首先，我们介绍了脊髓灰质炎、结核病和肝炎等疾病的观察性双胞胎一致性研究，这些研究表明了宿主遗传学的重要作用。我们回顾了特定基因改变与疟疾、克雅氏病（CJD）、人类免疫缺陷病毒（HIV）和诺如病毒易感性之间已确立的联系。最后，我们讨论了现代GWAS研究产生的新发现，这些发现表明主要组织相容性复合体（MHC）中的免疫变异对宿主遗传性传染病易感性有很大贡献。未来的大规模基因组研究有望深入了解免疫学与病原体之间的联系，并可能推动开发针对传染病预防和治疗的个性化基因组方法。
