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

• Published in: The Journal of infectious diseases Vol. 184; no. 3; p. 330
• Main Authors: Kun, J F, Mordmüller, B, Perkins, D J, May, J, Mercereau-Puijalon, O, Alpers, M, Weinberg, J B, Kremsner, P G
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.08.2001
• Subjects: 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
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/322037

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).