A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria.
Nat Genet
; 22(2): 145-50, 1999 Jun.
Article
em En
| MEDLINE
| ID: mdl-10369255
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Fatores de Transcrição
/
Regiões Promotoras Genéticas
/
Malária Falciparum
/
Malária Cerebral
/
Receptores do Fator de Necrose Tumoral
/
Predisposição Genética para Doença
/
Proteínas de Ligação a DNA
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Child
/
Humans
País/Região como assunto:
Africa
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Reino Unido