title: Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population.
abstract: BACKGROUND
  The first line anti-tubercular (anti-TB) treatment normally involves isoniazid, rifampicin, pyrazinamide, and ethambutol. Clearance of these drugs depends on the activity of several enzymes such as N-acetyl transferase 2, cytochrome P450 oxidase and glutathione S-transferase (GST). Some of these enzymes are highly polymorphic leading to significant inter-individual variation in their activity thereby increasing the risk of drug induced hepatotoxicity (DIH).
  
  
  OBJECTIVE
  To investigate the possible association of anti-TB DIH with genetic polymorphism of GST genes in Western Indian population.
  
  
  METHODS
  A prospective case-control study was undertaken on patients who received anti-TB treatment. Cases (n = 50) were distinguished from controls (n = 246) based on occurrence of DIH during anti-tubercular treatment. A multiplex polymerase chain reaction was employed to identify homozygous null mutation at GSTM1 and GSTT1 loci. Results. Homozygous null mutation in GSTM1 gene alone or in both GSTM1 and T1 genes was found to be significantly associated with anti-TB DIH at p < 0.02 and p < 0.007, respectively, in our study population.
  
  
  CONCLUSIONS
  This is the first study to report GSTM1 null and combined GSTM1 and T1 null genotypes to be risk factors of anti-TB DIH in Western Indian population. Screening of patients for these genotypes prior to anti-TB regimen would provide better control of hepatotoxicity.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai- 400076, India.
authors.forename: Vinod H
authors.initials: VH
authors.lastname: Gupta
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.forename: Deepak N
authors.initials: DN
authors.lastname: Amarapurkar
authors.forename: Preetha
authors.initials: P
authors.lastname: Sasi
authors.forename: Jyotsna M
authors.initials: JM
authors.lastname: Joshi
authors.forename: Rajiv
authors.initials: R
authors.lastname: Baijal
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: H R
authors.forename: Anjali D
authors.initials: AD
authors.lastname: Amarapurkar
authors.forename: Kalpana
authors.initials: K
authors.lastname: Joshi
authors.forename: Pramod P
authors.initials: PP
authors.lastname: Wangikar
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000378:metabolism; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1