Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by C190T and G560A mutations.
Pharmacogenetics
; 8(1): 67-72, 1998 Feb.
Article
en En
| MEDLINE
| ID: mdl-9511183
Human N-acetyltransferase type 1 (NAT1) catalyses the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens. Despite wide inter-individual variability in activity, historically, NAT1 was considered to be monomorphic in nature. However, recent reports of allelic variation at the NAT1 locus suggest that it may be a polymorphically expressed enzyme. In the present study, peripheral blood mononuclear cell NAT1 activity in 85 individuals was found to be bimodally distributed with approximately 8% of the population being slow acetylators. Subsequent sequencing of the individuals having slow acetylator status showed all to have either a C190T or G560A base substitution located in the protein encoding region of the NAT1 gene. The C190T base substitution changed a highly conserved Arg64, which others have shown to be essential for fully functional NAT1 protein. The C190T mutation has not been reported previously and we have named it NAT1 x 17. The G560A mutation is associated with the base substitutions previously observed in the NAT1 x 10 allele and this variant (NAT1 x 14) encodes for a protein with reduced acetylation capacity. A novel method using linear PCR and dideoxy terminators was developed for the detection of NAT1 x 14 and NAT1 x 17. Neither of these variants was found in the rapid acetylator population. We conclude that both the C190T (NAT1 x 17) and G560A (NAT1 x 14) NAT1 structural variants are involved in a distinct NAT1 polymorphism. Because NAT1 can bioactivate several carcinogens, this polymorphism may have implications for cancer risk in individual subjects.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Arilamina N-Acetiltransferasa
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Mutación Puntual
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pharmacogenetics
Año:
1998
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Reino Unido