Nitric oxide synthase 2(Lambaréné) (G-954C), increased nitric oxide production, and protection against malaria

J Infect Dis. 2001 Aug 1;184(3):330-6. doi: 10.1086/322037. Epub 2001 Jun 26.


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).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Child
  • DNA / blood
  • Female
  • Gabon
  • Gene Frequency*
  • Genetic Carrier Screening
  • Germany
  • Humans
  • Immunity, Innate / genetics*
  • Malaria / genetics*
  • Malaria / physiopathology
  • Male
  • Nigeria
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Papua New Guinea
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Senegal
  • Thailand


  • Nitric Oxide
  • DNA
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II