Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 classified 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 (5.9%) developed various ADRs following INH treatment. These reactions included nausea/vomiting, fever, visual impairment, and peripheral neuritis. We found a statistically significant difference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was significantly 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 findings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.
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PMID:Genotyping of the N-acetyltransferase2 polymorphism in the prediction of adverse drug reactions to isoniazid in Japanese patients. 1561 86

Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 26DNT, are carcinogenic in animal experiments. Humans are exposed to such chemicals in the workplace and in the environment. It is therefore important to develop methods to biomonitor people exposed to nitrotoluenes to prevent the potential harmful effects. For the present study, workers exposed to high levels of these chemicals were investigated. The external dose (air levels), the internal dose (urine metabolites), the biologically effective dose [hemoglobin (Hb) adducts and urine mutagenicity], and biological effects (chromosomal aberrations and health effects) were determined. Individual susceptibility was assessed by determining genetic polymorphisms of enzymes assumed to function in nitrotoluene metabolism, namely glutathione S-transferases (GSTM1, GSTT1, GSTP1), N-acetyltransferases (NAT1, NAT2), and sulfotransferases (SULT1A1, SULT1A2). The levels of urinary metabolites did not correlate with the air levels. The urinary mutagenicity levels determined in a subset of workers correlated with the levels of a benzylalcohol metabolite of DNT. The Hb-adducts correlated with the urine metabolites but not with the air levels. The frequency of chromosomal aberrations (gaps included) was increased (P < 0.05) in the exposed workers in comparison with a group of factory controls and correlated with the level of 24DNT Hb-adducts in young subjects (<31 years). The GSTM1-null genotype was significantly more prevalent in the controls than in the exposed group, which probably reflected an elevated susceptibility of the GSTM1-null genotype to adverse health effects of DNT exposure, such as nausea (odds ratio, 8.8; 95% confidence interval, 2.4-32.2). A statistically significant effect was seen for SULT1A2 genotype on a 24DNT Hb-adduct; GSTP1 genotype on a 2,4,6-trinitrotoluene Hb-adduct; and SULT1A1, SULT1A2, NAT1, GSTT1, and GSTP1 genotypes on chromosomal aberrations in the exposed workers.
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PMID:Biomarkers of exposure, effect, and susceptibility in workers exposed to nitrotoluenes. 1653 16