Determining the relation between N-acetyltransferase-2 acetylator phenotype and antituberculosis drug induced hepatitis by molecular biologic tests
Küçük Resim Yok
Tarih
2008
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Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Tüberküloz uzun süre kullanılması gereken ilaç kombinasyonlarıyla tedavi edilmekte ve izoniazid bu grup içerisindeki ana ilaçlar arasında yer almaktadır. Antitüberküloz ilaç kaynaklı hepatit, tüberküloz tedavisi sırasında karşılaşılan ciddi bir problemdir. N-asetiltransferaz-2 (NAT2), izoniazidi karaciğerde metabolize eden enzimdir ve bu yüzden hepatotoksisite gelişmesinde de etkisi olduğu düşünülmektedir. Ancak polimorfik NAT asetilasyon fenotipi ve antitüberküloz ilaç kaynaklı hepatit arasındaki ilişki hala tartışılmaktadır. Çalışmamızda, asetilatör durumunun antitüberküloz ilaç kaynaklı hepatit için risk faktörü olup olmadığının belirlenmesi amacıyla tüberküloz tanısı konan 100 olguda NAT2*5A, NAT2*6A, NAT2*7A/B ve NAT2*14A polimorfizmleri analiz edildi. Olguların 70’i tedavi sırasında hepatotoksisite gelişmeyen hastalardan seçildi ve kontrol grubu olarak hepatotoksisite gelişen olgulardan seçilen 30 hasta ise çalışma grubu olarak sınıflandırıldı. NAT2 polimorfizm sonuçlarına göre olgular üç fenotipik gruba ayrıldı. Kontrol grubunu oluşturan 70 olgunun 14 (%20)’ü hızlı, 37 (%52.9)’si orta, 19 (%27.10)’u yavaş; çalışma grubunu oluşturan 30 olgunun ise 3 (%10)’ü hızlı, 4 (%13.3)’ü orta ve 23 (%76.7)’ü yavaş asetilatör olarak belirlendi. Kontrol ve çalışma grupları asetilatör fenotiplerine göre karşılaştırıldığında aralarındaki farkın istatistiksel olarak anlamlı olduğu, yavaş asetilatör fenotipinin çalışma grubunda daha sık görüldüğü gözlendi. Sonuç olarak, moleküler biyolojik yöntemler kullanılarak NAT2 asetilatör fenotiplerinin analiz edilmesinin, tüberküloz tedavisi sırasında hepatotoksisite gelişebilecek olguların önceden saptanması ve tedavileri sırasında daha dikkatli takip edilmeleri konularında yarar sağlayacağı belirlendi.
Tuberculosis is treated with a group of drugs that need to be used over a long period of time and isoniazid is the major drug in this group. Antituberculosis drug-induced hepatitis is the most serious problem in tuberculosis treatment. The enzyme N-acetyltransferase-2 (NAT-2) metabolizes isoniazid in the liver so it is considered to cause hepatotoxicity. The association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is discussed. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms in 100 patients diagnosed with tuberculosis. 70 patients who did not develop hepatotoxicity were classified as the control group, and 30 patients who were diagnosed with antituberculosis drug-induced hepatitis were classified as the study group. NAT2 polymorphisms were divided into three phenotypic groups according to the analytical results obtained. Among the 70 patients constituting the control group; 14 (20%), 37 (52.9%), 19 (27.10%) patients were rapid, intermediate and slow acetylators respectively. In contrast, among the patients constituting the study group; 3 (10%), 4 (13.3%), 23 (76.7%) patients were rapid, intermediate and slow acetylators. The difference was statistically significant when the control and study groups were compared for their acetylator status. The proportion of slow acetylators was much higher in the study group. In conclusion, NAT2 acetylator phenotype analysis by molecular biology methods prior to medical treatment for tuberculosis, can be used both for determining the high-risk group of patients who may develop hepatotoxicity and for closer follow-up during treatment period.
Tuberculosis is treated with a group of drugs that need to be used over a long period of time and isoniazid is the major drug in this group. Antituberculosis drug-induced hepatitis is the most serious problem in tuberculosis treatment. The enzyme N-acetyltransferase-2 (NAT-2) metabolizes isoniazid in the liver so it is considered to cause hepatotoxicity. The association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is discussed. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms in 100 patients diagnosed with tuberculosis. 70 patients who did not develop hepatotoxicity were classified as the control group, and 30 patients who were diagnosed with antituberculosis drug-induced hepatitis were classified as the study group. NAT2 polymorphisms were divided into three phenotypic groups according to the analytical results obtained. Among the 70 patients constituting the control group; 14 (20%), 37 (52.9%), 19 (27.10%) patients were rapid, intermediate and slow acetylators respectively. In contrast, among the patients constituting the study group; 3 (10%), 4 (13.3%), 23 (76.7%) patients were rapid, intermediate and slow acetylators. The difference was statistically significant when the control and study groups were compared for their acetylator status. The proportion of slow acetylators was much higher in the study group. In conclusion, NAT2 acetylator phenotype analysis by molecular biology methods prior to medical treatment for tuberculosis, can be used both for determining the high-risk group of patients who may develop hepatotoxicity and for closer follow-up during treatment period.
Açıklama
Anahtar Kelimeler
Kulak, Burun, Boğaz, Solunum Sistemi
Kaynak
Tüberküloz ve Toraks
WoS Q Değeri
Scopus Q Değeri
Cilt
56
Sayı
1
