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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Nucleotide and haplotypic diversity of the NOS2A promoter region and its relationship to cerebral malaria
Human Genetics, Volume 112, No. 4, Year 2003
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Description
To assess the hypothesis that nitric oxide is critical in the pathogenesis of cerebral malaria, we analysed genetic variation in the proximal promoter region of NOS2A, the gene encoding inducible nitric oxide synthase. Sequencing 72 Gambian chromosomes revealed 11 single nucleotide polymorphisms in 2.5 kB (θ=8.6×10-4). Genotyping 104 nuclear families identified six common haplotypes. A single haplotype, uniquely defined by the NOS2A-1659T allele, was associated with cerebral malaria by a transmission disequilibrium test of 334 affected children and their parents (P=0.02). An independent case-control study of 505 different children from the same population replicated the allelic association with cerebral malaria (odds ratio: 1.31, P=0.04). Taken together these data indicate a weak but significant association of the NOS2A locus with susceptibility to cerebral malaria. Despite high linkage disequilibrium across the region studied, this association would not have been detected without the initial construction of a dense marker set for haplotype tagging. © Springer-Verlag 2003.
Authors & Co-Authors
Burgner, David Paul
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Usen, Stanley Ohunwu I.S.E.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Rockett, Kirk A.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Jallow, Muminatou
Gambia, Banjul
Medical Research Council Laboratories Gambia
Gambia, Banjul
Royal Victoria Teaching Hospital Gambia
Ackerman, Hans C.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Cervino, Alessandra C.L.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Pinder, Margaret
Gambia, Banjul
Medical Research Council Laboratories Gambia
Kwiatkowski, Dominic P.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Statistics
Citations: 35
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1007/s00439-002-0882-4
ISSN:
03406717
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Case-Control Study