Wodelo Wycliff, Wampande Eddie M, Andama Alfred, Kateete David Patrick, Ssekatawa Kenneth
Department of Immunology and Molecular Biology, School of Biomedical Science, College of Health Science, Makerere University, Kampala, Uganda.
Department of Veterinary Medicine, School of Veterinary Medicine and Animal Resources, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda.
Appl Clin Genet. 2024 Mar 29;17:33-46. doi: 10.2147/TACG.S457395. eCollection 2024.
Tuberculosis remains a global health concern, with substantial mortality rates worldwide. Genetic factors play a significant role in influencing susceptibility to tuberculosis. This review examines the current progress in studying polymorphisms within immune genes associated with tuberculosis susceptibility, focusing on African populations. The roles of various proteins, including Toll-like receptors, Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Non-Integrin, vitamin D nuclear receptor, soluble C-type lectins such as surfactant proteins A and D, C-type Lectin Domain Family 4 Member E, and mannose-binding lectin, phagocyte cytokines such as Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12, and Interleukin-18, and chemokines such as Interleukin-8, monocyte chemoattractant protein 1, Regulated upon activation, normal T-cell expressed and secreted are explored in the context of tuberculosis susceptibility. We also address the potential impact of genetic variants on protein functions, as well as how these findings align with the genetic polymorphisms not associated with tuberculosis. Functional studies in model systems provide insights into the intricate host-pathogen interactions and susceptibility mechanisms. Despite progress, gaps in knowledge remain, highlighting the need for further investigations. This review emphasizes the association of Single Nucleotide Polymorphisms with diverse aspects of tuberculosis pathogenesis, including disease detection and infection.
结核病仍然是一个全球卫生问题,在世界范围内导致相当高的死亡率。遗传因素在影响结核病易感性方面起着重要作用。本综述考察了与结核病易感性相关的免疫基因多态性研究的当前进展,重点关注非洲人群。探讨了多种蛋白质的作用,包括Toll样受体、树突状细胞特异性细胞间黏附分子3结合非整合素、维生素D核受体、可溶性C型凝集素如表面活性蛋白A和D、C型凝集素结构域家族4成员E以及甘露糖结合凝集素、吞噬细胞细胞因子如白细胞介素-1、白细胞介素-6、白细胞介素-10、白细胞介素-12和白细胞介素-18,以及趋化因子如白细胞介素-8、单核细胞趋化蛋白1、活化后调节、正常T细胞表达和分泌蛋白在结核病易感性背景下的作用。我们还讨论了基因变异对蛋白质功能的潜在影响,以及这些发现如何与不相关的结核病遗传多态性相匹配。模型系统中的功能研究为复杂的宿主-病原体相互作用和易感性机制提供了见解。尽管取得了进展,但知识空白仍然存在,这突出了进一步研究的必要性。本综述强调了单核苷酸多态性与结核病发病机制的多个方面的关联,包括疾病检测和感染。