Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort

Ru Chen; Jing Wang; Shaowen Tang; Yuan Zhang; Xiaozhen Lv; Shanshan Wu; Yinyin Xia; Peiyuan Deng; Yu Ma; Dehua Tu; Dafang Chen; Siyan Zhan

doi:10.1016/j.tube.2014.11.004

Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort

Tuberculosis (Edinb). 2015 Jan;95(1):68-74. doi: 10.1016/j.tube.2014.11.004. Epub 2014 Nov 27.

Authors

Ru Chen¹, Jing Wang¹, Shaowen Tang², Yuan Zhang³, Xiaozhen Lv⁴, Shanshan Wu¹, Yinyin Xia⁵, Peiyuan Deng⁶, Yu Ma⁷, Dehua Tu⁸, Dafang Chen¹, Siyan Zhan⁹

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
⁴ Clinical Research Division, Peking University Institute of Mental Health, and Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
⁵ Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
⁶ Center for Drug Reassessment, State Food and Drug Administration, Beijing, China.
⁷ Department of Tuberculosis Treatment, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
⁸ Department of Tuberculosis Treatment, Beijing Institute for Tuberculosis Control, Beijing, China.
⁹ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China. Electronic address: siyan-zhan@bjmu.edu.cn.

PMID: 25498879
DOI: 10.1016/j.tube.2014.11.004

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.

Keywords: Anti-tuberculosis drug; Drug transporter; Hepatotoxicity.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antitubercular Agents / adverse effects*
Chemical and Drug Induced Liver Injury / genetics*
China / ethnology
Female
Genotyping Techniques
Haplotypes / genetics
Humans
Linkage Disequilibrium / genetics
Liver-Specific Organic Anion Transporter 1
Male
Organic Anion Transporters / genetics*
Organic Anion Transporters, Sodium-Dependent / genetics*
Polymorphism, Single Nucleotide / genetics*
Symporters / genetics*
Tuberculosis, Pulmonary / drug therapy
Tuberculosis, Pulmonary / ethnology
Tuberculosis, Pulmonary / genetics*

Substances

Antitubercular Agents
Liver-Specific Organic Anion Transporter 1
Organic Anion Transporters
Organic Anion Transporters, Sodium-Dependent
SLCO1B1 protein, human
Symporters
sodium-bile acid cotransporter