Functional promoter haplotypes of interleukin-18 condition susceptibility to severe malarial anemia and childhood mortality.

Abstract

Severe malarial anemia (SMA) is a leading cause of morbidity and mortality in children residing in regions where plasmodium falciparum transmission is holoendemic. Although largely unexplored in children with SMA, interleukin-18 (Il-1S) is important for regulating innate and acquired immunity in inflammatory and infectious diseases. As such, we selected two functional single-nucleotide polymorphisms (SNPS) in the Il-18 promoter (-137G-C [rs187238J and-607-CA [rs1946518J) whose haplotypes encompass significant genetic variation due to the presence of strong linkage disequilibrium among these variants. The relationship between the genotypes/haplotypes, SMA (hemoglobin [HbJ,< 5.0 g/dlJ, and longitudinal clinical outcomes were then investigated in Kenyan children (n= 719). Multivariate logistic regression analyses controlling for age, gender, sickle cell trait …