Document Detail


A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria.
MedLine Citation:
PMID:  10369255     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.
Authors:
J C Knight; I Udalova; A V Hill; B M Greenwood; N Peshu; K Marsh; D Kwiatkowski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  22     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-06-29     Completed Date:  1999-06-29     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  145-50     Citation Subset:  IM    
Affiliation:
Molecular Infectious Diseases Group, Institute of Molecular Medicine, Oxford, UK. julian.knight@paediatrics.ox.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Child
DNA-Binding Proteins / metabolism*
Gambia
Gene Expression Regulation
Genetic Predisposition to Disease*
Genotype
Host Cell Factor C1
Humans
Kenya
Malaria, Cerebral / genetics*
Malaria, Falciparum / genetics*
Monocytes / metabolism
Octamer Transcription Factor-1
Plasmodium falciparum / pathogenicity
Polymorphism, Genetic*
Promoter Regions, Genetic*
Receptors, Tumor Necrosis Factor / genetics*
Reference Values
Regression Analysis
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/HCFC1 protein, human; 0/Host Cell Factor C1; 0/Octamer Transcription Factor-1; 0/POU2F1 protein, human; 0/Receptors, Tumor Necrosis Factor; 0/Transcription Factors
Comments/Corrections
Comment In:
Nat Genet. 1999 Jun;22(2):120-1   [PMID:  10369245 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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