CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

Abstract

Malaria remains a significant disease, causing epic health problems and challenges all over the world, especially in sub-Saharan Africa. CD209 and CD28 genes act as co-stimulators and regulators of the immune system, while the STAT6 gene has been reported to mediate cytokine-induced responses. Single nucleotide polymorphisms of these genes might lead to differential disease susceptibility among populations at risk for malaria, due to alterations in the immune response. We aim to identify key drivers of the immune response to malaria infection among the three SNPs: CD209 (rs4804803), CD28 (rs35593994) and STAT6 (rs3024974). After approval and informed consent, we genotyped blood samples from a total of 531 children recruited from Nigeria using the Taqman SNP genotyping assay and performed comparative analysis of clinical covariates among malaria-infected children. Our results reveal the CD209 (rs4804803) polymorphism as a susceptibility factor for malaria infection, significantly increasing the risk of disease among children, but not CD28 (rs35593994) or STAT6 (rs3024974) polymorphisms. Specifically, individuals with the homozygous mutant allele (rs4804803G/G) for the CD209 gene have a significantly greater susceptibility to malaria, and presented with higher mean parasitemia. This observation may be due to a defective antigen presentation and priming, leading to an ineffective downstream adaptive immune response needed to combat infection, as well as the resultant higher parasitemia and disease manifestation. We conclude that the CD209 gene is a critical driver of the immune response during malaria infection, and can serve as a predictor of disease susceptibility or a biomarker for disease diagnosis.

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects

“…Although polymorphisms located in the promoter region of CD209 are widely associated with the severity of various infectious diseases, (31,32,44,50,51) including tuberculosis, (30) such association has not yet been reported in leprosy. In view of the relevance of DC-SIGN in the recognition of antigens and activation of the immune response, and considering that the variations in genes that potentially influence the course of infections are largely population-dependent (52) we chose to investigate the association of candidate variants in the CD209 promoter region with the clinical manifestation of leprosy in a Brazilian population.…”

Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection

“…Additionally, in an experimental model with an advanced fibrosis resembling advanced hepatic fibrosis from human schistosomiasis, a role of Th17 response is demonstrated, whereas in human schistosomiasis, there is no clear understanding of what occurs in the later stages of fibrosis (9). Furthermore, the genetic background of the host might be involved in the modulation of immune response and pathogenesis development, as seen in many infectious diseases (10)(11)(12)(13)(14)(15). Thus, functional single nucleotide polymorphisms (SNPs) may be important as they may influence the gene expression or the structure of the corresponding protein (16).…”