title: IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks.
abstract: Using segregation analyses, control of malaria parasites has previously been linked to a major gene within the chromosomal region 5q31-33, but also to complex genetic factors in which effects are under substantial age-dependent influence. However, the responsible gene variants have not yet been identified for this chromosomal region. In order to perform association analyses of 5q31-33 locus candidate single nucleotide polymorphisms (SNPs), 1015 children were recruited at the age of 3 months and followed monthly until the age of 2 years in an area holoendemic for Plasmodium falciparum malaria in Ghana. Quantitative (incidence rates of malaria episodes) and qualitative phenotypes (i.e. 'more than one malaria episode' or 'not more than one malaria episode') were used in population- and family-based analyses. The strongest signal was observed for the interleukin 3 gene (IL3) SNP rs40401 (P = 3.4 × 10(-7), P(c)= 1.4 × 10(-4)). The IL3 genotypes rs40401(CT) and rs40401(TT) were found to exert a protective effect of 25% [incidence rate ratio (IRR) 0.75, P = 4.1 × 10(-5)] and 33% (IRR 0.67, P = 3.2 × 10(-8)), respectively, against malaria attacks. The association was confirmed in transmission disequilibrium tests (TDT, qTDT). The results could argue for a role of IL3 in the pathophysiology of falciparum malaria.
authors.affiliation: Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Meyer
authors.forename: Maria H
authors.initials: MH
authors.lastname: Calixto Fernandes
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Intemann
authors.forename: Benno
authors.initials: B
authors.lastname: Kreuels
authors.forename: Robin
authors.initials: R
authors.lastname: Kobbe
authors.forename: Christina
authors.initials: C
authors.lastname: Kreuzberg
authors.forename: Matilda
authors.initials: M
authors.lastname: Ayim
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Wibke
authors.initials: W
authors.lastname: Loag
authors.forename: Christa
authors.initials: C
authors.lastname: Ehmen
authors.forename: Samuel
authors.initials: S
authors.lastname: Adjei
authors.forename: Ohene
authors.initials: O
authors.lastname: Adjei
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Horstmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: May
mesh_terms: D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007377:Interleukin-3 / Q000235:genetics* / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence
chemical_list: D007377:Interleukin-3