TY - JOUR
T1 - Genotyping of the N-acetyltransferase2 Polymorphism in the Prediction of Adverse Drug Reactions to Isoniazid in Japanese Patients
AU - Hiratsuka, Masahiro
AU - Takekuma, Yoh
AU - Matsuura, Masaki
AU - Narahara, Kaori
AU - Inoue, Tomoko
AU - Ismail, Samar Hamdy
AU - Endo, Naomi
PY - 2002
Y1 - 2002
N2 - To investigate the association between NAT2 genotypes and the incidence of isoniazid (INH)-induced adverse reactions, in the hope of identifying a pharmacogenetic approach that could be useful in the prediction and prevention of adverse reactions in Japanese patients, we retrospectively studied the genotypes of NAT2 in 102 Japanese patients treated with INH (without rifampicin co-administration). The subjects were classiôed into three groups according to their genotypes: rapid-type, intermediate-type, and slow-type. The clinical conditions of the patients were followed-up in order to evaluate the development of any adverse drug reactions (ADRs) and correlate them with patient genotypes. Six out of the 102 patients (5.9z) developed various ADRs following INH treatment. These reactions included nauseaWvomiting, fever, visual impairment, and peripheral neuritis. We found a statistically signi ôcant diference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was signi ôcantly higher in the slow type than in the other two types, as 5 out of the 6 ADR patients were of the slow-type, and the other one was of the intermediate-type, while no patients of the rapid-type developed any ADRs. The results indicated that the genes coding for slow acetylation were associated with the incidence of serious ADRs following INH treatment. Our ôndings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.
AB - To investigate the association between NAT2 genotypes and the incidence of isoniazid (INH)-induced adverse reactions, in the hope of identifying a pharmacogenetic approach that could be useful in the prediction and prevention of adverse reactions in Japanese patients, we retrospectively studied the genotypes of NAT2 in 102 Japanese patients treated with INH (without rifampicin co-administration). The subjects were classiôed into three groups according to their genotypes: rapid-type, intermediate-type, and slow-type. The clinical conditions of the patients were followed-up in order to evaluate the development of any adverse drug reactions (ADRs) and correlate them with patient genotypes. Six out of the 102 patients (5.9z) developed various ADRs following INH treatment. These reactions included nauseaWvomiting, fever, visual impairment, and peripheral neuritis. We found a statistically signi ôcant diference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was signi ôcantly higher in the slow type than in the other two types, as 5 out of the 6 ADR patients were of the slow-type, and the other one was of the intermediate-type, while no patients of the rapid-type developed any ADRs. The results indicated that the genes coding for slow acetylation were associated with the incidence of serious ADRs following INH treatment. Our ôndings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.
KW - NAT2
KW - adverse drug reaction
KW - genetic polymorphism
KW - isoniazid
KW - pharmacogenetics
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U2 - 10.2133/dmpk.17.357
DO - 10.2133/dmpk.17.357
M3 - Article
AN - SCOPUS:18244393817
VL - 17
SP - 357
EP - 362
JO - Drug Metabolism and Pharmacokinetics
JF - Drug Metabolism and Pharmacokinetics
SN - 1347-4367
IS - 4
ER -