title: Interleukin (IL)-13 promoter polymorphisms (-7402 T/G and -4729G/A) condition susceptibility to pediatric severe malarial anemia but not circulating IL-13 levels.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya.
authors.forename: Winnie A
authors.initials: WA
authors.lastname: Okeyo
authors.forename: Elly O
authors.initials: EO
authors.lastname: Munde
authors.forename: Wilson
authors.initials: W
authors.lastname: Okumu
authors.forename: Evans
authors.initials: E
authors.lastname: Raballah
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Anyona
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.forename: John M
authors.initials: JM
authors.lastname: Ong'echa
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Perkins
authors.forename: Collins
authors.initials: C
authors.lastname: Ouma
mesh_terms: D000740:Anemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D002648:Child; D003710:Demography; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000097:blood* / Q000235:genetics*; D008288:Malaria / Q000097:blood / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: C578095:IL13 protein, human; D018793:Interleukin-13