Polymorphism Of PXR Gene Associated With The Increased Risk Of Drug-induced Liver Injury in Indonesian Pulmonary Tuberculosis Patients
| Main Authors: | Zazuli, Z., Barliana, M. I, Mulyani, Ully Adhie, Perwitasari, Dyah Aryani, Ng, H., Abdullah, R. |
|---|---|
| Format: | Article PeerReviewed Book |
| Bahasa: | eng |
| Terbitan: |
John Wiley and Sons Ltd (Wiley Online Library)
, 2015
|
| Subjects: | |
| Online Access: |
http://eprints.uad.ac.id/7194/1/Polymorphism_of_PXR_gene_associated_with_the_incre.pdf http://eprints.uad.ac.id/7194/ http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12325/abstract;jsessionid=D769D88D65E20616D6893CE604D6A704.f03t03 |
Daftar Isi:
- What is known and objective : Tuberculosis is still a major infectious disease in Indonesia. Patients are treated mostly using fixed-dose combination treatment in primary public health facilities. The incidence of antituberculosis drug-induced liver injury (AT-DILI) is approximately 10% among Indonesian tuberculosis patients who use standard fixed combination regimens during the intensive phase of treatment. However, information regarding genetic polymorphism associated with the increase risk of drug-induced liver injury is still limited. The aim of this study was to investigate pregnane X receptor (PXR) gene polymorphisms as one of the risk factors of AT-DILI. Methods : In this prospective cohort study, we recruited 106 adult patients diagnosed with pulmonary tuberculosis and treated with category I FDC (fixed-dose combination). The identification of SNP -25385C>T (rs3814055) was conducted by ARMS (amplification refractory mutation system). Hepatotoxicity was defined as ALT and/or AST levels above the normal threshold on the second, fourth and sixth months of monitoring during tuberculosis treatment. Results and discussions : The logistic regression analysis showed that patients with the TT genotype of PXR gene (rs3814055) significantly had a greater risk of AT-DILI (OR 8.89; 95% CI 1.36-57.93, P < 0.05), compared with those of wild-type CC genotype. What is new and conclusions : The result suggests that in Indonesian patients with tuberculosis, the risk of having AT-DILI was associated with TT genotype of the PXR gene.