Acta neurologica Scandinavica · 2006
Increased frequency of rapid acetylator genotypes in patients with brain astrocytoma and meningioma.
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Olivera M, Martínez C, Molina J A, Alonso-Navarro H, Jiménez-Jiménez F J, García-Martín E, Benítez J, Agúndez J A G
Аннотация
OBJECTIVES: The arylamine N-acetyltransferase (NAT2) is a polymorphic enzyme involved in deactivation and activation of carcinogens through N- and O-acetylation. We investigated the association between the genetic NAT2 polymorphism and brain tumors by analysis of genomic DNA from 71 brain tumor patients and 258 healthy controls.
MATERIALS AND METHODS: Seven single nucleotide polymorphisms of the NAT2 gene were studied by using allele-specific polymerase chain reaction amplification.
RESULTS: Ten different NAT2 allelic variants were identified in both patient and control groups. A higher number of individuals carrying functional NAT2 genes, and therefore with a rapid acetylation phenotype, was found in brain tumor patients vs healthy volunteers (OR 1.79, 95% CI 1.05-3.05; P < 0.05). This is observed either for patients suffering from meningioma or astrocytoma, and this is due to an increase of the wild-type NAT2*4 allelic variant frequency (OR 1.48, 95% CI 0.99-2.19), and a reduction of the commonest defective allelic variant NAT2*5B in the brain tumor patients, compared with healthy subjects (OR 0.54, 95% CI 0.37-0.80).
CONCLUSIONS: This observation indicates that NAT2 could be considered as a low-penetrance gene for brain tumors, and that individuals carrying rapid acetylation alleles are at increased risk of developing brain tumors.
MATERIALS AND METHODS: Seven single nucleotide polymorphisms of the NAT2 gene were studied by using allele-specific polymerase chain reaction amplification.
RESULTS: Ten different NAT2 allelic variants were identified in both patient and control groups. A higher number of individuals carrying functional NAT2 genes, and therefore with a rapid acetylation phenotype, was found in brain tumor patients vs healthy volunteers (OR 1.79, 95% CI 1.05-3.05; P < 0.05). This is observed either for patients suffering from meningioma or astrocytoma, and this is due to an increase of the wild-type NAT2*4 allelic variant frequency (OR 1.48, 95% CI 0.99-2.19), and a reduction of the commonest defective allelic variant NAT2*5B in the brain tumor patients, compared with healthy subjects (OR 0.54, 95% CI 0.37-0.80).
CONCLUSIONS: This observation indicates that NAT2 could be considered as a low-penetrance gene for brain tumors, and that individuals carrying rapid acetylation alleles are at increased risk of developing brain tumors.