[The relationship between carboxylesterase 1 gene polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity]

Zhonghua Nei Ke Za Zhi. 2012 Jul;51(7):524-30.
[Article in Chinese]

Abstract

Objective: To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CES1) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).

Methods: Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200:273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.

Results: In 4 tags of CES1 single nucleotide polymorphism (SNP), the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group(P = 0.0236). The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 (P = 0.044, OR = 0.649, 95%CI = 0.426 - 0.989, AC/AA) and rs1968753 (P = 0.048, OR = 0.556, 95%CI = 0.311 - 0.995, GG/AA). The diplotypes with 'CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P = 0.048, OR = 0.654, 95%CI = 0.430 - 0.996).

Conclusions: The genetic polymorphisms of CES1 might have significant association with ATBDIH. SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antitubercular Agents / toxicity*
  • Carboxylic Ester Hydrolases / genetics*
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Female
  • Genotype
  • Humans
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Tuberculosis / drug therapy*
  • Tuberculosis / pathology
  • Young Adult

Substances

  • Antitubercular Agents
  • Carboxylic Ester Hydrolases
  • CES1 protein, human