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Start Over Author "Peshu N" Journal genes and immunity
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4. A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production.

Author

Morahan G, Boutlis CS, Huang D, Pain A, Saunders JR, Hobbs MR, Granger DL, Weinberg JB, Peshu N, Mwaikambo ED, Marsh K, Roberts DJ, and Anstey NM

Subjects
Animals, Humans, Interleukin-12 Subunit p40, Kenya epidemiology, Malaria, Cerebral genetics, Molecular Sequence Data, Plasmodium immunology, Polymorphism, Genetic, Tanzania epidemiology, Interleukin-12 genetics, Malaria, Cerebral mortality, Nitric Oxide metabolism, Promoter Regions, Genetic, Protein Subunits genetics
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.

Published
2002
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