Mukadder ÇALIKOĞLU, Sevim KARAKAŞ, Hatice YILDIRIM, Aras Nurcan ATEŞ, Uğur ATİK, Lülüfer TAMER

Relationship between N-acetyl transferase-2 gene polymorphism and risk of bronchial asthma

Allerjik hastalıkları da içeren birçok patolojik durumun mekanizması hala belirsizdir. Asetilasyon oranı, allerjik hastalıkların gelişmesini etkileyen bir faktör olabilir. Çalışmamızda NAT2 genetik polimorfizminin bronşiyal astımın gelişmesinde bir rolü olup olmadığını araştırmayı amaçladık. Çalışma grubumuz 97 bronşiyal astım hastası (atopik n= 62; nonatopik n= 35) ve 104 sağlıklı bireyden oluşmaktadır. Kan EDTA içeren tüplerde toplandı ve DNA “high pure template preparation” kiti ile lökositlerden elde edildi. NAT2*5A, NAT2*6A, NAT2*7A/B ve NAT2*14A allelleri LightCycler-NAT2 mutasyon belirleme kiti kullanılarak LightCycler cihazında gerçek zamanlı PCR ile saptandı. Genotipe göre, mutant NAT2*5A (OR= 3.84, %95 GA= 1.08-13.6) ve NAT2*6A (OR= 5.27, %95 GA= 1.06-26.05) genotipinin bronşiyal astımın gelişmesinde yüksek bir risk faktörü olabileceğini bulduk. Fenotiplere göre gruplandırıldığında; yavaş NAT2*5A asetilatör fenotipi hızlı fenotip ile karşılaştırıldığında bronşiyal astım oluşturma riski iki kat daha fazladır (OR= 2.7, %95 GA= 1.07-6.97). Bu çalışmamız NAT2 yavaş asetilatörün astım hastalığına karşı hassaslığın bir belirteci olabileceğini göstermektedir. Çalışmadan elde edilen bulgular, hastalığın patogenezini açıklamaya çalışan teoriler için olabileceği gibi terapötik amaçlar için de kullanılabilir.

N-asetil transferaz-2 gen polimorfizmi ve bronşiyal astım riski arasındaki ilişki

There are still uncertainties as to the mechanism of many pathological conditions, among them allergic diseases. It has been suggest that acetylation rate may be a factor that influences the development of allergic diseases. The aim of the present study was to investigate further whether the genetic polymorphism of the NAT2 plays a role in susceptibility to bronchial asthma disease. Ninety-seven patients with bronchial asthma (atopic n= 62; non-atopic n= 35) and 104 healthy individuals were participated in this study. DNA was extracted from the leucocyte by high pure template preparation kit. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms of NAT2 were detected by using LightCycler-NAT2 mutation detection kit by real time PCR with LightCycler instrument. We found that mutant NAT2*5A (OR= 3.84, 95% CI= 1.08-13.6) and NAT2*6A (OR= 5.27, 95% CI= 1.06-26.05) genotype could be associated with a high risk for the development of bronchial asthma according to the genotype. After grouping phenotype, the risk for bronchial asthma was more than two times higher (OR= 2.7, 95% CI= 1.07-6.97) in individuals with the slow NAT2*5A acetylator phenotype compared to the fast phenotype. Our study suggests that the NAT2 slow acetylators may be a determinant in susceptibility to asthma disease. This finding may have implications for the theories for the pathogenesis of the disease as well as for therapeutic aspects.

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