INDUCIBLE NITRIC OXIDE SYNTHASE (NOS2) PROMOTER CCTTT REPEAT POLYMORPHISM: RELATIONSHIP TO IN VIVO NITRIC OXIDE PRODUCTION/NOS ACTIVITY IN AN ASYMPTOMATIC MALARIA-ENDEMIC POPULATION

CRAIG S. BOUTLIS International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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MAURINE R. HOBBS International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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ROBYN L. MARSH International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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MARY A. MISUKONIS International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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ARIANA N. TKACHUK International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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MOSES LAGOG International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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JENNIFER BOOTH International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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DONALD L. GRANGER International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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MOSES J. BOCKARIE International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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CHARLES S. MGONE International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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MARC C. LEVESQUE International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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J. BRICE WEINBERG International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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NICHOLAS M. ANSTEY International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Northern Territory University, Darwin, Northern Territory, Australia; Division of Infectious Diseases, Department of Internal Medicine, University of Utah and Veterans Administration Medical Centers, Salt Lake City, Utah; Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Flinders University, Northern Territory Clinical School, Darwin, Northern Territory, Australia

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DOI:
https://doi.org/10.4269/ajtmh.2003.69.569
Volume/Issue:
Volume 69: Issue 6
Page(s):
569–573
Restricted access
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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.

Author Notes

Copyright:
Copyright 2003 The American Society of Tropical Medicine 2003
Received:
13 May 2003
|
Accepted:
08 Aug 2003
|
Published Online:
Dec 2003
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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