Increased frequency of rapid acetylator genotypes in patients with brain astrocytoma and meningioma

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Abstract:

Olivera M, Martínez C, Molina JA, Alonso-Navarro H, Jiménez-Jiménez FJ, García-Martín E, Benítez J, Agúndez JAG. Increased frequency of rapid acetylator genotypes in patients with brain astrocytoma and meningioma.

Acta Neurol Scand 2006: 113: 322–326.

© 2006 The Authors Journal compilation © 2006 Blackwell Munksgaard. 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.

Keywords: NAT2; acetylation; brain tumor; polymorphisms

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0404.2006.00590.x

Affiliations: 1: Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain 2: Service of Neurology, University Hospital Doce de Octubre, Madrid, Spain 3: Department of Medicine-Neurology, University Hospital Principe de Asturias, Madrid, Spain 4: Department of Biochemistry & Molecular Biology, School of Sciences, University of Extremadura, Badajoz, Spain

Publication date: May 1, 2006

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