Publication: Atopik astımlı Türklerde NAT2 (N acetyltransferase-2) genotipi
Abstract
Allerjik hastalıklarda yapılan genetik çalışmalarda yavaş asetilasyonun bir risk faktörü olduğuna dair bilgiler bulunmaktadır. Vücudumuzda NAT2 (Nacetyltransferase2) yavaş ve hızlı olmak üzere iki farklı hızda çalışan; ilaç, xenobiotik ve karsinojenleri metabolize eden bir asetilasyon enzimidir. Bu hız farkı kişinin etnik yapısına göre değişiklik göstermektedir. Yapılan çalışmalarda NAT2 enziminin fenotipi ile genotipi arasında yakın korelasyon olduğu ve NAT2*4 allelinin homozigot veya heterozigot varlığının hızlı asetilasyona yol açtığı bilinmektedir. Günümüzde NAT2 enziminin yavaş asetilasyon tipi olanı allerjik hastalarda daha sık görülmektedir. Bu vakakontrol çalışmasında 57 akraba olmayan Türk atopik astımlı hasta ve 56 akraba olmayan sağlıklı kontrollerde yavaş ve hızlı asetilasyon gösteren NAT2 geninin sıklığının araştırılması amaçlanmıştır. Bu çalışmada NAT2 geninde iki farklı mutasyon (C282T ve T341C) varlığı araştırıldı. Yavaş asetilasyon astımlılarda %47 oranında saptanırken kontrol grubunda %43 hastada saptandı, arada istatistiksel anlamlı fark bulunmadı. Yaş, cinsiyet, eosinofili, solunum fonksiyon testi parametreleri ve serum IgE seviyelerinin bu asetilasyon hızıyla ilişkisi gösterilemedi. Bu çalışmanın sonucunda yavaş asetilasyon genotipinin atopik astımlı Türk hastalarda hastalık gelişmesinde genetik bir yatkınlık olarak saptanamadığı ifade edilebilir.
It has been shown that slow acetylation may be a risk factor that influences the development of allergic diseases. N-acetyltransferase2 (NAT2), an enzyme that degrades xenobiotics, carcinogens, and drugs, shows a bimodal distribution of rapid and slow acetylators with broad interethnic variation. It has been reported that there is close correlation between fenotyping and genotyping of NAT2. Homozygous or heterozygous NAT2*4 allelles are known to code for rapid acetylation. It has been known that NAT2 slow acetylation type is a risk factor for allergic diseases. In this case-control study, our aim was to assess the frequency of slow and rapid activity of NAT2 with asthma and asthma severity in the Turkish population. Turkish unrelated atopic subjects with asthma (n=57) and unrelated healthy subjects (n=56) were enrolled in this study. We evaluated two mutations (C282T and T341C) in NAT2 gene. The frequency of slow acetylators inferred from NAT2 genotype was not significantly different in asthmatic subjects (47%) and healthy subjects (43%). No significant association was found between NAT2 genotype and either age, sex, lung function test parameters, disease severity, duration, eosinophilia, serum IgE level within the asthmatics. This study suggests that the NAT2 (slow acetylation) genotype is not a marker of predisposition for atopic asthma in the Turkish population.
It has been shown that slow acetylation may be a risk factor that influences the development of allergic diseases. N-acetyltransferase2 (NAT2), an enzyme that degrades xenobiotics, carcinogens, and drugs, shows a bimodal distribution of rapid and slow acetylators with broad interethnic variation. It has been reported that there is close correlation between fenotyping and genotyping of NAT2. Homozygous or heterozygous NAT2*4 allelles are known to code for rapid acetylation. It has been known that NAT2 slow acetylation type is a risk factor for allergic diseases. In this case-control study, our aim was to assess the frequency of slow and rapid activity of NAT2 with asthma and asthma severity in the Turkish population. Turkish unrelated atopic subjects with asthma (n=57) and unrelated healthy subjects (n=56) were enrolled in this study. We evaluated two mutations (C282T and T341C) in NAT2 gene. The frequency of slow acetylators inferred from NAT2 genotype was not significantly different in asthmatic subjects (47%) and healthy subjects (43%). No significant association was found between NAT2 genotype and either age, sex, lung function test parameters, disease severity, duration, eosinophilia, serum IgE level within the asthmatics. This study suggests that the NAT2 (slow acetylation) genotype is not a marker of predisposition for atopic asthma in the Turkish population.