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Free Content iNOS promoter variants and severe malaria in Ghanaian children

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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 −1173C→T/CCTTT(13) increased fatality. These findings suggest that iNOS promoter haplotypes rather than single nucleotide polymorphisms are associated with malaria in Ghanaian children.
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Keywords: Plasmodium falciparum; inducible nitric oxide synthase promoter polymorphism; linkage disequilibrium; malaria; microsatellite

Document Type: Research Article

Affiliations: 1:  Institute of Tropical Medicine, Charité, Humboldt-University, Berlin, Germany 2:  School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana 3:  Institute for International Health Sciences, Humboldt-University, Berlin, Germany 4:  Bernsteinklinik Binz, Binz auf Rügen, Germany

Publication date: 2004-10-01

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