Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort.
Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model. There were no significant differences in genotype frequencies of ABCB11 between cases and controls. In the subgroup analysis, polymorphisms of rs2287616 were found to be associated with cholestatic/mixed pattern of liver injury under dominant and addictive model (OR = 3.84, 95% CI:1.16-12.75, P = 0.028 and OR = 2.51, 95% CI:1.12-5.62, P = 0.025, respectively), however the significance disappeared after Bonferroni correction. This study suggested that genetic variants of ABCB11 gene might contribute to anti-tuberculosis drug-induced cholestatic liver injury in Chinese patients. Studies in larger, varied populations are required to confirm these findings.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Ru
R
Chen
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Jing
J
Wang
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Shaowen
S
Tang
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
Yuan
Y
Zhang
Clinical Research Division, Peking University Institute of Mental Health, and Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
Xiaozhen
X
Lv
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Shanshan
S
Wu
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Zhirong
Z
Yang
Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Yinyin
Y
Xia
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Dafang
D
Chen
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Siyan
S
Zhan
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D000995:Antitubercular Agents