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Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes.

Publication ,  Journal Article
Levesque, MC; Hobbs, MR; O'Loughlin, CW; Chancellor, JA; Chen, Y; Tkachuk, AN; Booth, J; Patch, KB; Allgood, S; Pole, AR; Fernandez, CA ...
Published in: Hum Genet
February 2010

Nitric oxide (NO) mediates host resistance to severe malaria and other infectious diseases. NO production and mononuclear cell expression of the NO producing enzyme-inducible nitric oxide synthase (NOS2) have been associated with protection from severe falciparum malaria. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) and haplotypes in the NOS2 promoter, to identify associations of these haplotypes with malaria severity and to test the effects of these polymorphisms on promoter activity. We identified 34 SNPs in the proximal 7.3 kb region of the NOS2 promoter and inferred NOS2 promoter haplotypes based on genotyping 24 of these SNPs in a population of Tanzanian children with and without cerebral malaria. We identified 71 haplotypes; 24 of these haplotypes comprised 82% of the alleles. We determined whether NOS2 promoter haplotypes were associated with malaria severity in two groups of subjects from Dar es Salaam (N = 185 and N = 250) and in an inception cohort of children from Muheza-Tanga, Tanzania (N = 883). We did not find consistent associations of NOS2 promoter haplotypes with malaria severity or malarial anemia, although interpretation of these results was potentially limited by the sample size of each group. Furthermore, cytokine-induced NOS2 promoter activity determined using luciferase reporter constructs containing the proximal 7.3 kb region of the NOS2 promoter and the G-954C or C-1173T SNPs did not differ from NOS2 promoter constructs that lacked these polymorphisms. Taken together, these studies suggest that the relationship between NOS2 promoter polymorphisms and malaria severity is more complex than previously described.

Duke Scholars

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

February 2010

Volume

127

Issue

2

Start / End Page

163 / 182

Location

Germany

Related Subject Headings

  • Tanzania
  • Severity of Illness Index
  • Sequence Homology, Nucleic Acid
  • Sequence Analysis, DNA
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Nitric Oxide Synthase Type II
  • Mutation
  • Molecular Sequence Data
  • Malaria
 

Citation

APA
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ICMJE
MLA
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Levesque, M. C., Hobbs, M. R., O’Loughlin, C. W., Chancellor, J. A., Chen, Y., Tkachuk, A. N., … Weinberg, J. B. (2010). Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes. Hum Genet, 127(2), 163–182. https://doi.org/10.1007/s00439-009-0753-3
Levesque, Marc C., Maurine R. Hobbs, Charles W. O’Loughlin, Jennifer A. Chancellor, Youwei Chen, Ariana N. Tkachuk, Jennifer Booth, et al. “Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes.Hum Genet 127, no. 2 (February 2010): 163–82. https://doi.org/10.1007/s00439-009-0753-3.
Levesque MC, Hobbs MR, O’Loughlin CW, Chancellor JA, Chen Y, Tkachuk AN, et al. Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes. Hum Genet. 2010 Feb;127(2):163–82.
Levesque, Marc C., et al. “Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes.Hum Genet, vol. 127, no. 2, Feb. 2010, pp. 163–82. Pubmed, doi:10.1007/s00439-009-0753-3.
Levesque MC, Hobbs MR, O’Loughlin CW, Chancellor JA, Chen Y, Tkachuk AN, Booth J, Patch KB, Allgood S, Pole AR, Fernandez CA, Mwaikambo ED, Mutabingwa TK, Fried M, Sorensen B, Duffy PE, Granger DL, Anstey NM, Weinberg JB. Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes. Hum Genet. 2010 Feb;127(2):163–182.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

February 2010

Volume

127

Issue

2

Start / End Page

163 / 182

Location

Germany

Related Subject Headings

  • Tanzania
  • Severity of Illness Index
  • Sequence Homology, Nucleic Acid
  • Sequence Analysis, DNA
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Nitric Oxide Synthase Type II
  • Mutation
  • Molecular Sequence Data
  • Malaria