title: Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti-tuberculosis drug-induced hepatotoxicity.
abstract: BACKGROUND
  Host genetic factors that influence predisposition to anti-tuberculosis drug-induced hepatotoxicity (DIH) are not clear in the Indian population.
  
  
  OBJECTIVE
  To investigate the possible association of DIH with polymorphism at the RsaI site of the 5-prime untranslated region of CYP2E1 and GSTM1 'null' mutations.
  
  
  METHODS
  In this prospective study, 113 tuberculosis (TB) patients with DIH and 201 TB patients receiving anti-tuberculosis treatment without developing hepatotoxicity (non-DIH) constituted cases and controls, respectively. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyse genetic polymorphisms of CYP450 2E1 at the RsaI site and 'null' GSTM1 mutations. PCR-RFLP results were compared between 185 non-DIH and 105 DIH patients
  
  
  RESULTS
  A high frequency of c1c1 genotypes of CYP2E1 was commonly encountered, and the difference between DIH and non-DIH patients was not significant (75.14% vs. 77.14%). The genotypic distribution of c2c2 was significantly higher in the DIH than in the non-DIH group (4.8% vs. 0.5%, OR 8.58, P = 0.03). However, adjustment for age, sex and serum albumin differences yielded an OR of 2.75, making it non-significant (P = 0.26). Homozygous 'null' mutation frequencies at the GSTM1 gene in DIH and non-DIH patients were observed that were not significantly different (40% and 37%, respectively, P = 0.61).
  
  
  CONCLUSIONS
  RsaI variants of the CYP2E1 gene and GSTM1 'null' mutation were not associated with risk of DIH in a north Indian population.
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: B K
authors.initials: BK
authors.lastname: Jha
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: V
authors.initials: V
authors.lastname: Sreenivas
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: V
authors.initials: V
authors.lastname: Upadhyay
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: C
authors.initials: C
authors.lastname: Jaisinghani
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: R
authors.initials: R
authors.lastname: Singla
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: H K
authors.initials: HK
authors.lastname: Mishra
authors.affiliation: Departments of Internal Medicine, and Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Soneja
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D000995:Antitubercular Agents; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase