Sirisabhabhorn Kridsada, Chaijaroenkul Wanna, Na-Bangchang Kesara
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumthani 12121, Thailand.
Trop Med Infect Dis. 2021 Sep 24;6(4):174. doi: 10.3390/tropicalmed6040174.
Polymorphisms of the genes encoding proteins involved in immune functions and the binding of malaria parasites to human host cells have been the focus of research in recent years, aiming to understand malaria pathogenesis and case severity and to exploit this knowledge to assert control over malaria. This study investigated the genetic diversity of the human host genes encoding proteins that are involved in immune functions and malaria parasite binding, i.e., MCP1 (-2518), TGFβ1 (-509), TNFα (-308), IL4 (VNTR), IL6 (-174), IL10 (-3575), TLR4 (299), CD36 (-188), and ICAM1 (469) in patients with mono-infection of and infections in the multidrug-resistant areas along the Thai-Myanmar border. The association between gene polymorphisms and parasite density was also investigated. Genomic DNA (gDNA) of and were extracted from whole blood and dried blood spot (DBS). Gene amplification and genotyping were performed by PCR and PCR-RFLP analysis, respectively. Of these samples, 178 and 209 samples were, respectively, mono-infection with and . The ratio of : was 46%:54%. Results showed marked variation in the frequency distribution and patterns of the genotypes and gene alleles of the nine immune response genes or human host genes. The SNPs of TGFβ1, IL10 and ICAM1, were significantly associated with , but not parasite density. TGFβ1, IL10 and ICAM1, may play more significant roles in modulating than parasitemia. The prevalence of the genotypes and gene alleles of these genes, including their association with parasite density, may vary depending on patient ethnicity and endemic areas. Information obtained from each endemic area is essential for treatment strategies and the development of vaccines for malaria prophylaxis in specific areas.
近年来，编码参与免疫功能以及疟原虫与人类宿主细胞结合的蛋白质的基因多态性一直是研究的重点，旨在了解疟疾发病机制和病例严重程度，并利用这些知识来控制疟疾。本研究调查了编码参与免疫功能和疟原虫结合的蛋白质的人类宿主基因的遗传多样性，即泰国-缅甸边境多药耐药地区单纯感染 和 感染患者中的MCP1（-2518）、TGFβ1（-509）、TNFα（-308）、IL4（VNTR）、IL6（-174）、IL10（-3575）、TLR4（299）、CD36（-188）和ICAM1（469）。还研究了基因多态性与寄生虫密度之间的关联。从全血和干血斑（DBS）中提取 和 的基因组DNA（gDNA）。分别通过PCR和PCR-RFLP分析进行基因扩增和基因分型。在这些样本中，分别有178和209个样本为单纯感染 和 。 与 的比例为46%:54%。结果显示，九个免疫反应基因或人类宿主基因的基因型和基因等位基因的频率分布和模式存在显著差异。TGFβ1、IL10和ICAM1的单核苷酸多态性与 显著相关，但与 寄生虫密度无关。TGFβ1、IL10和ICAM1在调节 方面可能比调节 血症发挥更重要的作用。这些基因的基因型和基因等位基因频率，包括它们与寄生虫密度的关联，可能因患者种族和流行地区而异。从每个流行地区获得信息对于特定地区疟疾预防的治疗策略和疫苗开发至关重要。
