A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production

G. Morahan; C. S. Boutlis; D. Huang; A. Pain; J. R. Saunders; M. R. Hobbs; D. L. Granger; J. B. Weinberg; N. Peshu; E. D. Mwaikambo; K. Marsh; D. J. Roberts; N. M. Anstey

doi:10.1038/sj.gene.6363909

A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production

G. Morahan^*, C. S. Boutlis, D. Huang, A. Pain, J. R. Saunders, M. R. Hobbs, D. L. Granger, J. B. Weinberg, N. Peshu, E. D. Mwaikambo, K. Marsh, D. J. Roberts, N. M. Anstey

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

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 promoter 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 language	English (US)
Pages (from-to)	414-418
Number of pages	5
Journal	Genes and Immunity
Volume	3
Issue number	7
DOIs	https://doi.org/10.1038/sj.gene.6363909
State	Published - 2002
Externally published	Yes

Keywords

Immune regulation
Interleukin-12
Severe malaria
Th1-Th2

ASJC Scopus subject areas

Immunology
Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.gene.6363909

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Morahan, G., Boutlis, C. S., Huang, D., Pain, A., Saunders, J. R., Hobbs, M. R., Granger, D. L., Weinberg, J. B., Peshu, N., Mwaikambo, E. D., Marsh, K., Roberts, D. J., & Anstey, N. M. (2002). A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production. Genes and Immunity, 3(7), 414-418. https://doi.org/10.1038/sj.gene.6363909

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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 promoter 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.",

keywords = "Immune regulation, Interleukin-12, Severe malaria, Th1-Th2",

author = "G. Morahan and Boutlis, {C. S.} and D. Huang and A. Pain and Saunders, {J. R.} and Hobbs, {M. R.} and Granger, {D. L.} and Weinberg, {J. B.} and N. Peshu and Mwaikambo, {E. D.} and K. Marsh and Roberts, {D. J.} and Anstey, {N. M.}",

note = "Funding Information: This work was financially supported by the National Health and Medical Research Council of Australia and by a Special Program Grant from the NHMRC and the Juvenile Diabetes Research Foundation; National Institutes of Health RO1 AI41764, NHMRC Scholarship (CSB) and the Wellcome Trust, UK. DJR is a Howard Hughes International Research Scholar. No author has a commercial or other association that might pose a conflict of interest.",

year = "2002",

doi = "10.1038/sj.gene.6363909",

language = "English (US)",

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pages = "414--418",

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Morahan, G, Boutlis, CS, Huang, D, Pain, A, Saunders, JR, Hobbs, MR, Granger, DL, Weinberg, JB, Peshu, N, Mwaikambo, ED, Marsh, K, Roberts, DJ & Anstey, NM 2002, 'A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production', Genes and Immunity, vol. 3, no. 7, pp. 414-418. https://doi.org/10.1038/sj.gene.6363909

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T1 - A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production

AU - Morahan, G.

AU - Boutlis, C. S.

AU - Huang, D.

AU - Pain, A.

AU - Saunders, J. R.

AU - Hobbs, M. R.

AU - Granger, D. L.

AU - Weinberg, J. B.

AU - Peshu, N.

AU - Mwaikambo, E. D.

AU - Marsh, K.

AU - Roberts, D. J.

AU - Anstey, N. M.

N1 - Funding Information: This work was financially supported by the National Health and Medical Research Council of Australia and by a Special Program Grant from the NHMRC and the Juvenile Diabetes Research Foundation; National Institutes of Health RO1 AI41764, NHMRC Scholarship (CSB) and the Wellcome Trust, UK. DJR is a Howard Hughes International Research Scholar. No author has a commercial or other association that might pose a conflict of interest.

PY - 2002

Y1 - 2002

N2 - 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 promoter 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.

AB - 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 promoter 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.

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ER -

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

Keywords

ASJC Scopus subject areas

UN SDGs

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