Association of N‐acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms with antituberculosis drug‐induced hepatotoxicity in Western India

• DOI: 10.1111/jgh.12194
• Publication Date: 2013-03-13T23:04:13Z
• Authors: Vinod H Gupta; Deepak N Amarapurkar; Meenakshi Singh; Preetha Sasi; Jyotsna M Joshi; Rajiv Baijal; Praveenkumar H Ra...; Anjali D Amarapurkar; Kalpana Joshi; Pramod P Wangikar
• Keywords: Adult; Male; 0301 basic medicine; Genotype; Arylamine N-Acetyltransferase; Population; Antitubercular Agents; Predisposition; India; Genetic Polymorphisms; Polymerase Chain Reaction; Cohort Studies; Induced Hepatitis; 03 medical and health sciences; Gene Frequency; 616; Isoniazid; Risk-Factors; Humans; Point Mutation; Genetic Predisposition to Disease; Liver-Injury; Cyp2e1 Gene; Polymorphism, Genetic; Cytochrome P-450 CYP2E1; Middle Aged; Nat2; 3. Good health; Slow Acetylator; Logistic Models; N-Acetyltransferase-2; Susceptibility; Tb Patients; Female; Drug-Induced Hepatotoxicity; Chemical and Drug Induced Liver Injury; Polymorphism, Restriction Fragment Length

Abstract Background and Aim Tuberculosis ( TB ) is a major public health problem in I ndia. Despite the treatment availability monitoring, drug‐induced hepatotoxicity DIH serious concern can lead to discontinuation of treatment. Anti‐ well known aggravate because pharmacokinetic pharmacodynamic interactions. Genetic polymorphism drug‐metabolizing enzyme genes an important factor that predisposes certain fraction population toxicity. The purpose this study was assess association N ‐acetyltransferase 2 NAT cytochrome P 450 E 1 CYP gene with anti‐ W estern ndian population. Methods A prospective cohort 215 patients taking against performed. genotypes were determined using polymerase chain reaction restriction fragment length methods. Logistic regression model used calculate odds ratio at 95% confidence interval their respective values. Results risk significantly higher slow acetylator SA than intermediate rapid (odds ratio: 2.3, = 0.01). We also observed homozygous point mutation position 481, associated < haplotype 2*4 seems provide protection compared non‐ 0.04). However, we did not find significant between . Conclusion Increased susceptibility isoniazid INH )‐induced due presence demonstrated genotyping therefore serve as tool for identifying predisposed