Abstract
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 Plasmodium falciparum and Plasmodium vivax 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 P. falciparum and P. vivax 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 P. falciparum and P. vivax. The ratio of P. falciparum: P. vivax 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 P. falciparum, but not P. vivax parasite density. TGFβ1, IL10 and ICAM1, may play more significant roles in modulating P. falciparum than P. vivax 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.
Highlights
The present study investigated the genetic diversity of the human host genes involved in immune response [monocyte chemoattractant protein 1 (MCP1)-2518, transforming growth factor β1 (TGFβ1)-509, tumor necrosis factor α (TNFα)-308, interleukin 4 (IL4) variable number tandem repeat (VNTR), interleukin 6 (IL6)-174, and interleukin 10 (IL10)-3575], as well as those involved in malaria parasite binding [toll-like receptor 4 (TLR4)-299, cluster of differentiation 36 (CD36)-188, and intercellular adhesion molecule 1 (ICAM1)-469] in patients with mono-infection of P. falciparum or P. vivax, residing in the multidrug-resistant areas along the Thai-Myanmar border [5]
The Hardy–Weinberg Equilibrium (HWE) deviation observed with TGFβ1, TNFα, IL10, CD36 and ICAM1 could be due to gene mutation, population migration, and/or selection of genotypes/alleles of the study populations
The genes involved in host immune response and binding of the malaria parasite, TGFβ1, IL10 and ICAM1 may play a more significant role in malaria parasitemia in P. falciparum than in P. vivax infection
Summary
Malaria remains one of the major global public health problems despite the declining incidence in recent years. In 2018, 3.2 billion people were at risk of malaria infection, with an estimated 219 million cases and 435,000 malaria-related deaths [1]. Over 90% of death cases were reported from sub-Saharan Africa, most of which were children under five years of age. Five species of malaria parasite infect humans, i.e., Plasmodium falciparum, P
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