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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

Winnie A Okeyo1, Elly O Munde1, Wilson Okumu2, Evans Raballah3, Samuel B Anyona2, John M Vulule4, John M Ong’echa45, Douglas J Perkins56 and Collins Ouma157*

Author Affiliations

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

2 Department of Medical Biochemistry, School of Medicine, Maseno University, Maseno, Kenya

3 Department of Medical Laboratory Sciences, School of Health Sciences, Masinde Muliro University of Science and Technology, Kakamega, Kenya

4 Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya

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

6 Center for Global Health, Department of Internal Medicine, University of New Mexico, Health Sciences Centre, Albuquerque, NM, USA

7 Directorate of Research, Publications and Consultancies, Maseno University, Kisumu-Busia Road, Private Bag, Maseno, Kenya

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BMC Immunology 2013, 14:15  doi:10.1186/1471-2172-14-15

Published: 25 March 2013


In holoendemic Plasmodium falciparum transmission areas such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dL, with any density parasitemia] is the most common clinical manifestation of severe malaria resulting in high rates of pediatric morbidity and mortality in these regions. Previous studies associated interleukin (IL)-13 with pathogenesis of different infectious diseases, including P. falciparum malaria. However, the functional roles of polymorphic variants within the IL-13 promoter in conditioning susceptibility to SMA remain largely unexplored. As such, the association between the IL-13 variants -7402 T/G (rs7719175) and -4729G/A (rs3091307) and susceptibility to SMA was determined in children (n = 387) presenting with clinical symptoms of falciparum malaria and resident in a holoendemic transmission region in western Kenya. Our results indicated no difference in the proportions of individual genotypes among children presenting with non-SMA (n = 222) versus SMA (n = 165). Similarly, there was no associations between the individual genotypes (-7402 T/G and -4729G/A) and SMA. Additional analyses, however, revealed that proportions of individuals with -7402 T/-4729A (TA) haplotype was significantly higher in children presenting with SMA than non-SMA group (P = 0.043). A further multivariate logistic regression analyses, controlling for confounding factors, demonstrated that carriage of the TA haplotype was associated with increased susceptibility to SMA (OR; 1.564, 95% CI; 1.023-2.389, P = 0.039). In addition, circulating levels of IL-13 were comparable between the clinical groups as well as across genotypes and haplotypes. Collectively, findings presented here suggest that haplotypes within the IL-13 promoter at -7402 T/G and -4729G/A may modulate SMA pathogenesis, but do not affect circulating IL-13 levels.

IL-13; Promoter polymorphisms; Haplotypes; Severe malaria anemia