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Nitric Oxide Synthase 2 Lambaréné (G‐954C), Increased Nitric Oxide Production, and Protection against Malaria

2001; Oxford University Press; Volume: 184; Issue: 3 Linguagem: Inglês

10.1086/322037

1537-6613

Jürgen F. J. Kun, Benjamin Mordmüller, Douglas J. Perkins, Jürgen May, Odile Mercereau‐Puijalon, Michael Alpers, J. Brice Weinberg, Peter G. Kremsner,

Renin-Angiotensin System Studies

A point mutation in the promoter of the nitric oxide synthase 2 gene (NOS2), termed NOS2Lambaréné (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 NOS2Lambaréné carriers) were monitored for 4 years, to assess the rates of malarial attacks in the 2 groups; carriers of the NOS2Lambaréné polymorphism were significantly less likely to experience malarial attacks than were others (⁠P=.002⁠). The distribution of the NOS2Lambaréné 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).