title: Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort.
abstract: This study investigated the association between genetic variants in two hepatic uptake transporter genes (SLCO1B1 and SLC10A1) and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) in a Chinese cohort. The frequencies and distributions of single nucleotide polymorphisms (SNPs) and haplotypes of these genes were compared among 89 incident ATDH cases and 356 matched ATDH-free controls using a multivariate conditional logistic regression analysis. After correction for potential confounding factors, significant differences were found in polymorphism of rs4149014 under an addictive model (P = 0.008) and a recessive model (P = 0.016). The result of haplotype analysis suggested that patients carrying at least one SLCO1B1*15 haplotype had a higher risk of ATDH (odds ratio (OR) = 1.74, 95% confidence intervals (CI): 1.04-2.90, P = 0.034) in comparison with those carrying SLCO1B1*1a or SLCO1B1*1b haplotypes. These findings indicate that genetic variants of SLCO1B1 are associated with the development of ATDH in Chinese population.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Research Division, Peking University Institute of Mental Health, and Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Center for Drug Reassessment, State Food and Drug Administration, Beijing, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Deng
authors.affiliation: Department of Tuberculosis Treatment, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Tuberculosis Treatment, Beijing Institute for Tuberculosis Control, Beijing, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Tu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors.forename: Dafang
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. Electronic address: siyan-zhan@bjmu.edu.cn.
authors.forename: Siyan
authors.initials: S
authors.lastname: Zhan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D002681:China / Q000208:ethnology; D005260:Female; D060005:Genotyping Techniques; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D027981:Symporters / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C503999:SLCO1B1 protein, human; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: Anti-tuberculosis drug; Drug transporter; Hepatotoxicity