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

BMC Infectious Diseases

Research Article

Winnie A. Okeyo¹  Collins Ouma²  Elly O. Munde³  John M. Ong’echa⁴  Douglas J. Perkins⁵  Evans Raballah⁶ 

[1]Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya

[2]Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya

[3]Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[4]Ideal Research Centre, Kisumu, Kenya

[5]Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya

[6]University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[7]University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[8]Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[9]University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[10]Department of Internal Medicine, Centre for Global Health, Health Sciences Centre, University of New Mexico, Albuquerque, NM, USA

[11]University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

[12]Department of Medical Laboratory Science, School of Public Health, Biomedical Sciences and Technology, Masinde Muliro University of Science and Technology, Kakamega, Kenya

关键词: Il-23R;    Exon;    Genotypes;    Haplotypes;   

DOI  :  10.1186/s12879-017-2404-y

 received in 2016-12-23, accepted in 2017-04-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundImproved 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.MethodsSince 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.ResultsLogistic 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).ConclusionResults 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.

【 授权许可】

CC BY   
© The Author(s). 2017