Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population



Título del documento: Association of GST null genotypes with anti-tuberculosis drug induced hepatotoxicity in Western Indian population
Revue: Annals of hepatology
Base de datos: PERIÓDICA
Número de sistema: 000415630
ISSN: 1665-2681
Autores: 1
2
3
1
4
5
5
6
7
2
Instituciones: 1Indian Institute of Technology Bombay, Department of Biosciences and Bioengineering, Bombay, Maharashtra. India
2Indian Institute of Technology Bombay, Department of Chemical Engineering, Bombay, Maharashtra. India
3Bombay Hospital and Medical Research Centre, Department of Gastroenterology and Hepatology, Bombay, Maharashtra. India
4TN Medical College, Department of Pulmonary Medicine, Bombay, Maharashtra. India
5Jagjivanram Western Railway Hospital, Department of Gastroenterology and Hepatology, Bombay, Maharashtra. India
6TN Medical College, Department of Pathology, Bombay, Maharashtra. India
7Symbiosis School of Biomedical Sciences, Department of Biotechnology, Pune, Maharashtra. India
Año:
Periodo: Nov-Dic
Volumen: 12
Número: 6
Paginación: 959-965
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Analítico, descriptivo
Resumen en inglés 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). Aim. To investigate the possible association of anti-TB DIH with genetic polymorphism of GST genes in Western Indian population. Material and 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
Disciplinas: Medicina
Palabras clave: Farmacología,
Gastroenterología,
Fármacos antituberculosos,
Hepatotoxicidad,
Polimorfismo genético
Keyword: Medicine,
Gastroenterology,
Pharmacology,
Antituberculosis agents,
Hepatotoxicity,
Genetic polymorphism
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