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 journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)1074-1080
Number of pages7
JournalTropical Medicine and International Health
Volume9
Issue number10
DOIs
StatePublished - Oct 2004
Externally publishedYes

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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