[The effect of GST M1 and GST T1 gene mutations on anti-tuberculous drug induced hepatic injury].
OBJECTIVE
To study the relationship between the polymorphisms of GST M1 and GST T1 genes and anti-tuberculous drug induced hepatic injury (ADIH).


METHODS
A 1:1 matched case-control study was carried out. One hundred and six patients [age (49 +/- 19) years, 73 men and 33 women] fulfilling the criteria of ADIH during the 3 month follow-up after the initiation of anti-tuberculous therapy were included, while 106 cases [age (49 +/- 19) years, 73 men and 33 women] without any hepatic injury served as the controls. The genotypes of GST M1 and GST T1 genetic polymorphisms were detected by polymerase chain reaction (PCR) in patients who received anti-tuberculosis therapy. Using SPSS 11.5 for windows software, univariate and multivariate conditional logistic analyses were conducted for studying the relationship between the polymorphisms and ADIH.


RESULTS
Univariate analysis demonstrated that the "null" genotype of GST M1 gene occurred in 50 (47.2%) of the cases, more frequent than in the controls [25 (23.6%)], with a crude OR (95%CI) 2.786 (1.513 - 5.130). No significant association was observed between ADIH and GST T1 polymorphism. Among the risk factors analyzed, body mass index and alcohol drinking were significantly associated with ADIH. In the multivariate analysis, a significant association between ADIH and the "null" genotype of GST M1 existed, after adjusting for body mass index and drinking status, adjusted OR (95%CI) being 3.022 (1.540 - 5.926). Again, no significant association was observed between GST T1 polymorphism and ADIH.


CONCLUSIONS
This study demonstrated that patients carrying GST M1-"null" genotype may be susceptible to ADIH.
Guo
Mei
M
Department of Epidemiology and Health Statistics, North China Coal Medical University, Tangshan 063000, China.
Sun
Yong-Hong
YH
Li
Shi-Ming
SM
Wang
Dong
D
Liu
Qian
Q
Zhang
Xi-Ying
XY
Liu
Xiao-Xiao
XX
Feng
Fu-Min
FM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D055815:Young Adult
D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1