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01 September 1997

Molecular genotyping of the arylamine N-acetyltransferase polymorphism in children

Elżbieta Zielińska, Wojciech Niewiarowski, Jerzy Bodalski, Grzegorz Rębowski, Iwona Matusiak

Med Sci Monit 1997; 3(5): CR661-668 :: ID: 501566


Mutations of the N-acetyltransferase-encoding gene (NAT2) underlie inter-individual and inter-ethnic differences in pharmacokinetics of arylamines and hydrazines and belong to factors that account for the increased risk of cancer and idiosyncratic reactions to drugs.In the present study we determined frequencies of the NAT2 genotype and the NAT2 gene mutations in the population of children from central Poland in order to develop a prophylactic system against the adverse drug effects and to highlight the genetic basis of the elevated risk of diseases caused by environmental factors. To this end, genomic DNA was isolated from one to two millilitres of blood collected from 197 Polish children hospitalised with various infections. Polymerase chain reaction (PCR) was then carried out followed by the restriction mapping with the KpnI, TaqI, DdeI, and BamHI endonucleases in order to identify the six alleles at the NAT2 gene locus: wild-type 'fast acetylator' allele (wt), and five mutant 'slow acetylator' alleles designated 5A (481C→T), 5B (481C→T;803A→G), 5C (803A→G), 6A (590G→A), and 7B (857G→A). The following allele frequencies were detected: wt - 22.3%, 5A - 19.0%, 5B - 18.8%, 5C - 8.6%, 6A - 22.3%, and 7B - 9.4%. The most frequent mutations were 803G and 481T, immediately followed by mutations 590A and 857A. The wild-type allele was detected in 75 (38%) children and the slow acetylation genotype was found in 122 (62%) children. These frequencies compare well with the distribution of NAT2 in the children populations from other parts of Europe. Altogether, the present results indicate that determination of the NAT2 genotype is a useful method for detection of the acetylation defect and for estimating the risk of idiosyncratic disorders and hypersensitivity to drugs in children.

Keywords: N-Acetyltransferase, genotype NAT2, Pharmacogenetics, Polymerase Chain Reaction



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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750