title: Association of CYP2B6 gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a Chinese population.
abstract: Antituberculosis drug-induced hepatotoxicity (ATDH) remains a common and severe challenge in tuberculosis (TB) chemotherapy. A growing number of studies have revealed that genetic polymorphisms affect an individual's susceptibility to ATDH. The aim of this study was to explore the role of cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene polymorphisms in the development of ATDH in Chinese TB patients.
  
  
  
  CYP2B6*6 genotypes were determined in TB patients with and without ATDH. Association between polymorphisms and risk of ATDH was estimated by multiple logistic regression analysis.
  
  
  
  A total of 343 eligible TB patients (166 with ATDH; 177 without ATDH) were included in this study. Analysis of all subjects revealed no statistical differences in genotype distribution between the two groups. However, the CYP2B6 *6/*6 genotype was significantly associated with decreased risk of ATDH in the male subgroup (P=0.039, OR=0.097, 95% CI: 0.011-0.885). Furthermore, in male patients, the presence of the CYP2B6*6 allele was significantly higher in the non-ATDH group compared with the ATDH group (26.2% vs. 15.5%, P=0.020, OR=0.522, 95% CI: 0.301-0.903).
  
  
  
  This study is the first to demonstrate an association between CYP2B6 polymorphisms and the risk of ATDH in the Chinese population. We have shown that males who have the CYP2B6 *6/*6 genotype may be less susceptible to the development of ATDH. Further studies are required to confirm this genetic association result.
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Shou-Quan
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Ming-Gui
authors.initials: MG
authors.lastname: Wang
authors.affiliation: Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Wang
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: jianqing_he@scu.edu.cn.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: He
mesh_terms: D000328:Adult; D000483:Alleles; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D056486:Chemical and Drug Induced Liver Injury / Q000208:ethnology / Q000209:etiology* / Q000235:genetics / Q000382:microbiology; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics* / Q000378:metabolism; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D007538:Isoniazid; D012293:Rifampin
keywords: CYP2B6; Drug-induced hepatotoxicity; Polymorphisms; Tuberculosis