GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis drugs in Koreans.
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.
Kim
Sang-Heon
SH
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>
Kim
Sang-Hoon
SH
Yoon
Ho Joo
HJ
Shin
Dong Ho
DH
Park
Sung Soo
SS
Kim
Youn-Seup
YS
Park
Jae-Seuk
JS
Jee
Young Koo
YK
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
D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1