ArticleHuman genetics2010
Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes.
Article in Human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon.Malaria journal · 2023Article
- Association of TNF-Alpha, MBL2, NOS2, and G6PD with Malaria Outcomes in People in Southern Ghana.Genetics research · 2022Article
- Divergent Genetic Regulation of Nitric Oxide Production between C57BL/6J and Wild-Derived PWD/PhJ Mice Controls Postactivation Mitochondrial Metabolism, Cell Survival, and Bacterial Resistance in Dendritic Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Association of NOS2A gene polymorphisms with susceptibility to bovine tuberculosis in Chinese Holstein cattle.PloS one · 2021Article
- iNOS polymorphism modulates iNOS/NO expression via impaired antioxidant and ROS content in P. vivax and P. falciparum infection.Redox biology · 2018Article
- Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.Malaria journal · 2017Article
- Relationship of bovine NOS2 gene polymorphisms to the risk of bovine tuberculosis in Holstein cattle.The Journal of veterinary medical science · 2016Article
- Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.Clinical and molecular hepatology · 2015Review
- Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion molecules thrombospondin and E-selectin are risk factors for Plasmodium falciparum malaria in India.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2015Article
- Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2015Article
- NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.Infection and immunity · 2014Article
- A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.Human genetics · 2013Article
- The host genetic diversity in malaria infection.Journal of tropical medicine · 2012Article
- Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans.The Journal of infectious diseases · 2010Article
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
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.
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