iNOS promoter variants and severe malaria in Ghanaian children

Jakob P. Cramer; Frank P. Mockenhaupt; Stephan Ehrhardt; Jana Burkhardt; Rowland N. Otchwemah; Ekkehardt Dietz; Sabine Gellert; Ulrich Bienzle

doi:10.1111/j.1365-3156.2004.01312.x

iNOS promoter variants and severe malaria in Ghanaian children

Jakob P. Cramer, Frank P. Mockenhaupt, Stephan Ehrhardt, Jana Burkhardt, Rowland N. Otchwemah, Ekkehardt Dietz, Sabine Gellert, Ulrich Bienzle

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

29 Scopus citations

Abstract

Nitric oxide is an important mediator in the host defence against Plasmodium falciparum malaria. It has antiparasitic effects in vitro. However, its role in clinical disease remains controversial. Polymorphisms in the inducible nitric oxide synthase promoter (iNOS; -954G→C, -1173C→T, -2.6 kb CCTTT_(n) microsatellite) may influence susceptibility to and severity of malaria. We tested this hypothesis in a case-control study among Ghanaian children with severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy controls. In this study, the respective frequencies of iNOS -954G→C and -1173C→T did not differ between groups but ≥13 microsatellite copies were associated with SM. -954G→C and -1173C→T were in linkage disequilibrium with CCTTT₍₈₎ and CCTTT ₍₁₃₎, respectively. -954G→C/CCTTT₍₈₎ protected against hyperparasitaemia whereas -1,173C→T/CCTTT₍₁₃₎ increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.

Original language	English (US)
Pages (from-to)	1074-1080
Number of pages	7
Journal	Tropical Medicine and International Health
Volume	9
Issue number	10
DOIs	https://doi.org/10.1111/j.1365-3156.2004.01312.x
State	Published - Oct 2004
Externally published	Yes

Keywords

Inducible nitric oxide synthase promoter polymorphism
Linkage disequilibrium
Malaria
Microsatellite
Plasmodium falciparum

ASJC Scopus subject areas

Parasitology
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1111/j.1365-3156.2004.01312.x

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title = "iNOS promoter variants and severe malaria in Ghanaian children",

abstract = "Nitric oxide is an important mediator in the host defence against Plasmodium falciparum malaria. It has antiparasitic effects in vitro. However, its role in clinical disease remains controversial. Polymorphisms in the inducible nitric oxide synthase promoter (iNOS; -954G→C, -1173C→T, -2.6 kb CCTTT(n) microsatellite) may influence susceptibility to and severity of malaria. We tested this hypothesis in a case-control study among Ghanaian children with severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy controls. In this study, the respective frequencies of iNOS -954G→C and -1173C→T did not differ between groups but ≥13 microsatellite copies were associated with SM. -954G→C and -1173C→T were in linkage disequilibrium with CCTTT(8) and CCTTT (13), respectively. -954G→C/CCTTT(8) protected against hyperparasitaemia whereas -1,173C→T/CCTTT(13) increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.",

keywords = "Inducible nitric oxide synthase promoter polymorphism, Linkage disequilibrium, Malaria, Microsatellite, Plasmodium falciparum",

author = "Cramer, {Jakob P.} and Mockenhaupt, {Frank P.} and Stephan Ehrhardt and Jana Burkhardt and Otchwemah, {Rowland N.} and Ekkehardt Dietz and Sabine Gellert and Ulrich Bienzle",

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AU - Cramer, Jakob P.

AU - Mockenhaupt, Frank P.

AU - Ehrhardt, Stephan

AU - Burkhardt, Jana

AU - Otchwemah, Rowland N.

AU - Dietz, Ekkehardt

AU - Gellert, Sabine

AU - Bienzle, Ulrich

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N2 - Nitric oxide is an important mediator in the host defence against Plasmodium falciparum malaria. It has antiparasitic effects in vitro. However, its role in clinical disease remains controversial. Polymorphisms in the inducible nitric oxide synthase promoter (iNOS; -954G→C, -1173C→T, -2.6 kb CCTTT(n) microsatellite) may influence susceptibility to and severity of malaria. We tested this hypothesis in a case-control study among Ghanaian children with severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy controls. In this study, the respective frequencies of iNOS -954G→C and -1173C→T did not differ between groups but ≥13 microsatellite copies were associated with SM. -954G→C and -1173C→T were in linkage disequilibrium with CCTTT(8) and CCTTT (13), respectively. -954G→C/CCTTT(8) protected against hyperparasitaemia whereas -1,173C→T/CCTTT(13) increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.

AB - Nitric oxide is an important mediator in the host defence against Plasmodium falciparum malaria. It has antiparasitic effects in vitro. However, its role in clinical disease remains controversial. Polymorphisms in the inducible nitric oxide synthase promoter (iNOS; -954G→C, -1173C→T, -2.6 kb CCTTT(n) microsatellite) may influence susceptibility to and severity of malaria. We tested this hypothesis in a case-control study among Ghanaian children with severe malaria (SM) and asymptomatic parasitaemia, respectively, and in healthy controls. In this study, the respective frequencies of iNOS -954G→C and -1173C→T did not differ between groups but ≥13 microsatellite copies were associated with SM. -954G→C and -1173C→T were in linkage disequilibrium with CCTTT(8) and CCTTT (13), respectively. -954G→C/CCTTT(8) protected against hyperparasitaemia whereas -1,173C→T/CCTTT(13) increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.

KW - Inducible nitric oxide synthase promoter polymorphism

KW - Linkage disequilibrium

KW - Malaria

KW - Microsatellite

KW - Plasmodium falciparum

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iNOS promoter variants and severe malaria in Ghanaian children

Abstract

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