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Pourmohamadi, Nasir, Pour Abdollah Toutkaboni, Mihan, Hayati Roodbari, Nasim, Tabarsi, Payam, Baniasad, Shadi. (1402). Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study. سامانه مدیریت نشریات علمی, 48(5), 474-483. doi: 10.30476/ijms.2023.96145.2765
Nasir Pourmohamadi; Mihan Pour Abdollah Toutkaboni; Nasim Hayati Roodbari; Payam Tabarsi; Shadi Baniasad. "Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study". سامانه مدیریت نشریات علمی, 48, 5, 1402, 474-483. doi: 10.30476/ijms.2023.96145.2765
Pourmohamadi, Nasir, Pour Abdollah Toutkaboni, Mihan, Hayati Roodbari, Nasim, Tabarsi, Payam, Baniasad, Shadi. (1402). 'Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study', سامانه مدیریت نشریات علمی, 48(5), pp. 474-483. doi: 10.30476/ijms.2023.96145.2765
Pourmohamadi, Nasir, Pour Abdollah Toutkaboni, Mihan, Hayati Roodbari, Nasim, Tabarsi, Payam, Baniasad, Shadi. Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study. سامانه مدیریت نشریات علمی, 1402; 48(5): 474-483. doi: 10.30476/ijms.2023.96145.2765

Association of Cytochrome P450 2E1 and N-Acetyltransferase 2 Genotypes with Serum Isoniazid Level and Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Cross-Sectional Study

Iranian Journal of Medical Sciences
مقاله 5، دوره 48، شماره 5، آذر 2023، صفحه 474-483    اصل مقاله (520.45 K)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2023.96145.2765
نویسندگان
Nasir Pourmohamadi1؛ Mihan Pour Abdollah Toutkaboni2؛ Nasim Hayati Roodbari1؛ Payam Tabarsi3؛ Shadi Baniasad* 4
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2Molecular Medicine Laboratory, Department of Pathology, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
4Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
چکیده
Background: Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) genes on serum isoniazid level and drug-induced hepatotoxicity. 
Methods: A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample t test, Chi square test, or Fisher’s exact test. P<0.05 was considered statistically significant.
Results: A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). NAT2*4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of NAT2*5 and NAT2*6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). NAT2*4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and CYP2E1 C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001). 
Conclusion: Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of NAT2 SA polymorphism. Determining NAT2 and CYP2E1 genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity.

تازه های تحقیق

Nasir Pourmohamadi (Google Scholar)

Shadi Baniasadi (Google Scholar)

کلیدواژه‌ها
Hepatotoxicity؛ Isoniazid؛ Polymorphism؛ NAT2؛ CYP2E1
سایر فایل های مرتبط با مقاله
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