Nitric oxide synthase 2(Lambaréné) (G-954C), increased nitric oxide production, and protection against malaria.
A point mutation in the promoter of the nitric oxide synthase 2 gene (NOS2), termed NOS2(Lambaréné) (NOS2-G954C), protects heterozygous carriers against severe malaria as effectively as the sickle cell trait. In a prospective longitudinal study, 841 individual infections of initially 200 children (151 wild-type vs. 49 NOS2(Lambaréné) carriers) were monitored for 4 years, to assess the rates of malarial attacks in the 2 groups; carriers of the NOS2(Lambaréné) polymorphism were significantly less likely to experience malarial attacks than were others (P=.002). The distribution of the NOS2(Lambaréné) polymorphism was investigated in malaria-endemic areas. It was found to be present with the highest frequency in Africa and at a lower frequency in Asia. Ex vivo studies showed that cells isolated from people with this polymorphism have a 7-fold higher baseline NOS activity, compared with the levels detected in cells from subjects with the wild-type gene (P=.003).
Kun
J F
JF
Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, D-72074 Tübingen, Germany. juergen.kun@uni-tuebingen.de
Mordmüller
B
B
Perkins
D J
DJ
May
J
J
Mercereau-Puijalon
O
O
Alpers
M
M
Weinberg
J B
JB
Kremsner
P G
PG
D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000097:blood; D005260:Female; D005681:Gabon; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005858:Germany; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008288:Malaria / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009549:Nigeria; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010219:Papua New Guinea; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012675:Senegal; D013785:Thailand
D009569:Nitric Oxide; D004247:DNA; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II