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

摘要

In holoendemic Plasmodium falciparum transmission areas such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb)?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.