Show simple item record

dc.contributor.authorWere, T.
dc.contributor.authorGichuki, C.W.
dc.contributor.authorOng'echa, J. M.
dc.contributor.authorOuma, Collins
dc.contributor.authorAnyona, S.B.
dc.contributor.authorKempaiah, P.
dc.contributor.authorRaballah, E.
dc.contributor.authorDavenport, G. C.
dc.contributor.authorKonah, S.N.
dc.contributor.authorVulule, J.M.
dc.contributor.authorHittner, James B.
dc.contributor.authorPerkins, D. J.
dc.date.accessioned2013-12-28T06:51:03Z
dc.date.available2013-12-28T06:51:03Z
dc.date.issued2011
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/8238
dc.description.abstractSevere 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, glucose-6-phosphate dehydrogenase (G6PD) deficiency, HIV-1, and bacteremia revealed that carriage of the -607AA genotype was associated with protection against SMA (odds ratio [ORJ = 0.440 [95% confidence interval {CI} =0.21 to 0.90J, P = 0.031) in children with acute infection. In contrast, carriers of the -137G/-607C (GC) haplotype had increased susceptibility to SMA (OR =2.050 [95% CI = 1.04 to 4.05J, P = 0.039). Measurement of IL-18 gene expression in peripheral blood leukocytes demonstrated that elevated IL-18 transcripts were associated with reduced hemoglobin concentrations (p = -0.293, P = 0.010) and that carriers of the "susceptible" GC haplotype had elevated IL-18 transcripts (p= 0.026). Longitudinal investigation of clinical outcomes over a 3-year follow-up period revealed that carriers of the rare CC haplotype (-1% frequency) had 5.76 times higher mortality than noncarriers (p = 0.001). Results presented here demonstrate that IL-18 promoter haplotypes that condition elevated IL-18 gene products during acute infection are associated with increased risk of SMA. Furthermore, carriage of the rare CC haplotype significantly increases the risk of childhood mortallty.en_US
dc.language.isoenen_US
dc.publisherPubMeden_US
dc.titleFunctional promoter haplotypes of interleukin-18 condition susceptibility to severe malarial anemia and childhood mortality.en_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record