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Interleukin (IL)-13 promoter polymorphisms (-7402 T/G and -4729G/A) condition susceptibility to pediatric severe malarial anemia but not circulating IL-13 levels

<div>Okeyo Winnie A</div>, <div>Munde Elly O</div>, <div>Okumu Wilson</div>, <div>Raballah Evans</div>, <div>Anyona Samuel B</div>, <div>Vulule John M</div>, <div>Ong’echa John M</div>, <div> 9 PAGES (7339 WORDS) Biomedical Science Article/Essay
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Abstract

Background: Improved understanding of the molecular mechanisms involved in pediatric severe malarial anemia(SMA) pathogenesis is a crucial step in the design of novel therapeutics. Identification of host genetic susceptibility factors in immune regulatory genes offers an important tool for deciphering malaria pathogenesis. The IL-23/IL-17immune pathway is important for both immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R). However, the impact of IL-23R variants on SMA has not been fully elucidated.
Methods: Since variation within the coding region of IL-23R may influence the pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511 (C/T), and SMA (Hb < 6.0 g/dL) was examined in children(n = 369, aged 6–36 months) with P. falciparum malaria in a holoendemic P. falciparum transmission area.
Results: Logistic regression analysis, controlling for confounding factor of anemia, revealed that individual genotypes ofIL-23R rs1884444 (G/T) [GT; OR = 1.34, 95% CI = 0.78–2.31, P=0.304 and TT; OR = 2.02, 95% CI = 0.53–7.74, P=0.286] andIL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59–11.86, P=0.202 and TT; OR = 1.66, 95% CI = 0.84–3.27, P=0.142] were not associated with susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT) haplotype, consisting of both mutant alleles, was associated with increased susceptibility to SMA (OR = 1.12, 95% CI = 1.07–4.19, P=0.030).
Conclusion: Results presented here demonstrate that a haplotype of non-synonymous IL-23R variants increases susceptibility to SMA in children of a holoendemic P. falciparum transmission area.Keywords: Il-23R, Exon, Genotypes, Haplotypes
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