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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.

Original publication

DOI

10.1038/sj.gene.6363909

Type

Journal article

Journal

Genes Immun

Publication Date

11/2002

Volume

3

Pages

414 - 418

Keywords

Animals, Humans, Interleukin-12, Interleukin-12 Subunit p40, Kenya, Malaria, Cerebral, Molecular Sequence Data, Nitric Oxide, Plasmodium, Polymorphism, Genetic, Promoter Regions, Genetic, Protein Subunits, Tanzania