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STAT6 Promoter Polymorphism is Essential for Malaria Infection and Suppression of Parasitemia Among Infected Children
Author(s) -
Seamans Brooke,
Liou Gialeigh,
Ojurongbe Olusola,
Thomas Bolaji
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.808.2
Subject(s) - parasitemia , genotype , malaria , biology , single nucleotide polymorphism , immunology , allele , snp , minor allele frequency , plasmodium falciparum , genetics , gene
Significant morbidity and mortality among children remain the most consequential outcome of malaria infection in sub‐Saharan Africa, with host genetic variants reported to modulate infectivity and regulation of disease markers. Effector T cells are essential for a proper immune response, such responses ameliorated by regulatory T cells, which are encoded by genes implicated in cytokine cross regulation. One such gene is the signal transducer and activator of transcription 6 (STAT6), whose intronic (rs3024974) single nucleotide polymorphism (SNP), is suspected in malaria pathogenesis. To this end, regulatory SNP of the STAT6 gene was genotyped in a cohort of P. falciparum malaria infected (n=106) and uninfected, control children (n=225), ages 1–5 years, recruited from Nigeria. The genotypic distribution of rs3024974 was in Hardy‐Weinberg equilibrium, among all groups. Even though the wild type genotype ( rs3024974CC ) was commoner in both groups; 83.0% (infected) versus 70.7% (uninfected); the percentile frequency of rs3024974TT genotype of STAT6 was significantly higher among uninfected children compared to infected (4.9% versus 1.0% respectively). In addition, the minor allele rs3024974T was doubly prevalent among uninfected controls than infected children (17.1% versus 8.9% respectively; p =0.01). Significantly, children with the mutant genotype ( rs3024974TT ) were less likely to develop clinical malaria (OR 0.19; 95% CI=0.00–1.31), with the odds increased tenfold among children with wild‐type genotype (OR=2.03; 95% CI=1.10–3.86). This observation was further confirmed when examining markers of disease among infected children, with parasitemia significantly less (tenfold reduction) in those with the mutant genotype (mean parasite count: 2,986 parasites/ml of blood) versus children with wild‐type genotype (mean parasite count: 30,242 parasites/ml of blood). Despite the fact there were differences in other markers (age, weight, packed cell volume, temperature) based on rs3024974 variants, these differences were not significant. We conclude that STAT‐6 promoter polymorphism rs3024974 is a susceptibility factor for malaria infection and significant downregulation of P. falciparum parasitemia levels among infected children. Support or Funding Information Laboratory Support and Faculty Development Award, College of Health Sciences and Technology, Rochester Institute of Technology This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .