title: GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis drugs in Koreans.
abstract: Adverse reactions induced by antituberculosis drugs (ATD) often result in serious morbidities, impeding scheduled treatment and cure. In the development of ATD-induced adverse reactions, glutathione S-transferase has been suggested to play a protective role as an intracellular scavenger by conjugating toxic reactive metabolites of ATD. This study examined the association of null mutations in GST enzyme genes (GSTT1 and GSTM1) with the development of ATD-induced hepatitis and cutaneous reactions. We compared the frequencies of GSTT1 and GSTM1 null mutations in 57 patients with hepatitis, 94 patients with cutaneous adverse reactions, and 190 ATD-tolerant controls. The frequency of null mutations in GSTT1 and GSTM1 in patients with ATD-induced hepatitis was not significantly different from that of controls (59.6% vs. 54.2% and 45.6% vs. 54.7%, respectively). Additionally, no significant difference was observed in the frequency of either null mutation in patients with ATD-induced cutaneous reactions, including maculopapular eruption, compared with controls (58.5% vs. 54.1% for GSTT1 and 59.6% vs. 54.6% for GSTM1). These findings indicate that GSTT1 and GSTM1 null mutations are not associated with the development of ATD-induced hepatitis or cutaneous reactions in this Korean population, and suggest that glutathione S-transferase enzymes do not play important roles in the pathogenesis of these conditions.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Haengdang-dong 17, Seongdong-gu, Seoul 133-792, Korea. sangheonkim@hanyang.ac.kr <sangheonkim@hanyang.ac.kr>
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Joo
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Shin
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Park
authors.forename: Youn-Seup
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae-Seuk
authors.initials: JS
authors.lastname: Park
authors.forename: Young Koo
authors.initials: YK
authors.lastname: Jee
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D004252:DNA Mutational Analysis; D003875:Drug Eruptions / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1