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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya

Authors: Elly O. Munde, Evans Raballah, Winnie A. Okeyo, John M. Ong’echa, Douglas J. Perkins, Collins Ouma

Published in: BMC Infectious Diseases | Issue 1/2017

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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-17 immune 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 of IL-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] and IL-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 increase susceptibility to SMA in children of a holoendemic P. falciparum transmission area.
Appendix
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Metadata
Title
Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya
Authors
Elly O. Munde
Evans Raballah
Winnie A. Okeyo
John M. Ong’echa
Douglas J. Perkins
Collins Ouma
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2404-y

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