iNOS promoter variants and severe malaria in Ghanaian children.
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 > or =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.
Institute of Tropical Medicine, Charité, Humboldt-University, Berlin, Germany. jakob.cramer@charite.de
Jakob P
JP
Cramer
Frank P
FP
Mockenhaupt
Stephan
S
Ehrhardt
Jana
J
Burkhardt
Rowland N
RN
Otchwemah
Ekkehardt
E
Dietz
Sabine
S
Gellert
Ulrich
U
Bienzle
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008288:Malaria / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II