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Descrizione dell’editore

The arylamine N-acetyltransferase 2 (NAT2 [5]; E.C. 2.3.1.5) is a polymorphic enzyme involved in the metabolism of drugs and aromatic amines. About 50% of white individuals are classified as slow acetylators, and these individuals show impaired metabolism of many therapeutically useful arylamine and hydrazine drugs (1). In patients with tuberculosis who receive isoniazid, determination of the N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2) genotype or phenotype has been proposed as a method for predicting adverse reactions as well as before the concomitant administration of drug combinations such as procainamide-phenytoin or doxycycline-rifampin (1-3). In addition, the NAT2 polymorphism modulates the risk for the development of bladder (4, 5) and liver cancer (6). Diverse NAT2 genotyping methods have been developed, including amplification-restriction (7) and allele-specific methods (8), real-time PCR (9), and high-throughput microarrays (10). All of these genotyping methods simultaneously analyze 2 alleles (i.e., the paternal and the maternal allele). This characteristic is a major source of uncertainty in the case of NAT2 analysis, because 2 or more enzyme-inactivating mutations can be located in 1 allele, leaving the other allele intact, or the mutations can be distributed between the 2 alleles, leading to a lack of functional NAT2 alleles (1, 5). In fact, rather than indicating real genotypes, most genotyping method results indicate the sum of 2 haplotypes (diplotypes), and many such diplotypes can represent different genotypes with different functional consequences. This fact, together with the increasing importance of haplotypes in association studies (11), makes it necessary to determine specific haplotype combinations.

GENERE
Scienza e natura
PUBBLICATO
2008
1 agosto
LINGUA
EN
Inglese
PAGINE
12
EDITORE
American Association for Clinical Chemistry, Inc.
DIMENSIONE
173
KB

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