title: A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production.
abstract: Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. morahan@wehi.edu.au
authors.forename: G
authors.initials: G
authors.lastname: Morahan
authors.forename: C S
authors.initials: CS
authors.lastname: Boutlis
authors.forename: D
authors.initials: D
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Pain
authors.forename: J R
authors.initials: JR
authors.lastname: Saunders
authors.forename: M R
authors.initials: MR
authors.lastname: Hobbs
authors.forename: D L
authors.initials: DL
authors.lastname: Granger
authors.forename: J B
authors.initials: JB
authors.lastname: Weinberg
authors.forename: N
authors.initials: N
authors.lastname: Peshu
authors.forename: E D
authors.initials: ED
authors.lastname: Mwaikambo
authors.forename: K
authors.initials: K
authors.lastname: Marsh
authors.forename: D J
authors.initials: DJ
authors.lastname: Roberts
authors.forename: N M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000818:Animals; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D007630:Kenya / Q000453:epidemiology; D016779:Malaria, Cerebral / Q000235:genetics / Q000401:mortality*; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D010961:Plasmodium / Q000276:immunology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000235:genetics*; D013636:Tanzania / Q000453:epidemiology
chemical_list: D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12; D009569:Nitric Oxide