Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population

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Date

2003

Journal Title

Journal ISSN

Volume Title

Publisher

The American journal of tropical medicine and hygiene

Abstract

Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTTn) 2.5 kilobases upstream from the NOS2 transcription start site, and two single nucleotide substitutions: G→ C at position -954 (G-954C), and C→ T at position -1173 (C-1173T). Although hypothesized to influence NO production in vivo, the functional relevance of (CCTTT)n and G-954C is uncertain because disease association studies have yielded inconsistent results. This study found no association between CCTTT repeat number and levels of plasma NO metabolites or peripheral blood mononuclear cell NOS activity in a cohort of asymptomatic malaria-exposed coastal Papua New Guineans 1–60 years old. This suggests that (CCTTT)n does not independently influence NOS2 transcription in vivo. Neither the G-954C nor the C-1173T polymorphisms were identified in this population, indicating the variability and complexity of selection for NOS2 promoter polymorphisms in different malaria-endemic populations.

Description

Keywords

Nitric Oxide Synthase, Asymptomatic malaria-endemic, Polymorphisms

Citation

Boutlis, C.S., Hobbs, M.R., Marsh, R.L., Misukonis, M.A., Tkachuk, A.N., Lagog, M., Booth, J., Granger, D.L., Bockarie, M.J., Mgone, C.S. and Levesque, M.C., 2003. Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population. The American journal of tropical medicine and hygiene, 69(6), pp.569-573.

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