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. 2021 Sep 24;6(4):174.
doi: 10.3390/tropicalmed6040174.

Genetic Diversity of Human Host Genes Involved in Immune Response and the Binding of Malaria Parasite in Patients Residing along the Thai-Myanmar border

Kridsada Sirisabhabhorn  1 , Wanna Chaijaroenkul  1   2 , Kesara Na-Bangchang  1   2   3
Affiliations

Genetic Diversity of Human Host Genes Involved in Immune Response and the Binding of Malaria Parasite in Patients Residing along the Thai-Myanmar border

Kridsada Sirisabhabhorn et al. Trop Med Infect Dis. .

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.

Keywords: CD36; ICAM1; IL10; IL4 (VNTR); IL6; MCP1; Plasmodium falciparum; Plasmodium vivax; TGFβ1; TLR4; TNFα.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
The PCR-RFLP products for (a) MCP1 polymorphism at position −2518: AA (940 bp), GG (650 bp) and GA (940 and 650 bp) genotypes, (b) TGFβ1 polymorphism at position −509: CC (178 bp), TT (159 bp) and TC (178 and 159 bp) genotypes, (c) TNFα polymorphism at position −308: AA (117 bp), GA (117 and 97) and GG (97 bp) genotypes, (d) IL6 polymorphism at position −174: GG (233 bp) and GC (233 and 122 bp) genotypes, (e) IL10 polymorphism at position −3575: AA (228 bp), TA (228, 121 and 107 bp) and TT (121 and 107 bp) genotypes, (f) IL4 VNTR: 1,1 (253 bp), 2,2 (183 bp) and 1,2 (253 and 183 bp) genotypes, (g) TLR4 polymorphism at position 299: AA (249) and AG (249 and 223 bp) genotypes, (h) CD36 polymorphism at position −188: GG (213 bp), TG (213, 148 bp) and TT (148) genotypes, and (i) ICAM1 polymorphism at position 469: AA (223 bp), GG (136), and AG (223, 136) genotypes.
Figure 2
Figure 2
The relationship between the genotypes of the nine genes under investigation and Log (parasite density) (/μL) in (a) P. falciparum and (b) P. vivax infections.
Figure 2
Figure 2
The relationship between the genotypes of the nine genes under investigation and Log (parasite density) (/μL) in (a) P. falciparum and (b) P. vivax infections.
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