Astımda Genetik Faktörler ve Gen-Çevre Etkileşimi

Year 2017, Volume: 9 Issue: 2, 48 - 62, 15.03.2017

Doç. Ph. Dr. Çağatay Karaaslan

Abstract

Öz

Astım genetik faktörlerin, çevresel faktörlerin ve epigenetik faktörlerin etkileşimi sonucu ortaya çıkan hava yollarında daralma ve enflamasyonla karakterize bir hastalıktır.  Astım kompleks hastalıkların tipik özelliklerini taşımaktadır. Yani astım, gelişiminde her birinin etkisi küçük olan birçok gendeki değişimler sonucunda ortaya çıkmaktadır. Astım genetiğinde kullanılan tekniklerin kapasitesi yaygın genetik değişkenlikleri belirlemeyle sınırlıdır. Yaygın genetik değişkenlerin hastalık fenotipine katkıları ise oldukça azdır ve tek gen hastalıklarından elde edilen deneyimin ortaya koyduğu gibi nadir değişkenliklerin hastalık gelişimine olan etkileri oldukça fazladır. Genetik çalışmalarda kullanılan teknolojide gerçekleştirilen büyük ilerlemeler has-talığı daha iyi anlamamızı sağlamıştır. Ancak hala çözüm bekleyen konular vardır.Astım ve alerjik hastalıkların ardında yatan genetik faktörleri belirlemeye yönelik olarak yapılan tüm çalışmalar resmin tam olarak anlaşılabilmesi için çeşitli genler ve değişkenliklerin birbirleri, makro ve mikro çevre ile etkileşimlerinin ve epigenetik faktörlerin belirlenmesi gerekliliğini ortaya koymuştur. Günümüzde, nadir görülen genetik değişkenliklerin, insersiyon ve delesyonların, hatta kopya sayısı değişikliklerinin belirlenmesine olanak sağlayan, tüm genomun veya protein kodlayan gen bölgelerinin tamamının yeniden dizilenmesi tekniği, astım gibi kompleks hastalıkların genetiğinin aydınlatılmasında yeni bir yöntem olarak kullanılmaktadır. Bu teknolojiye  “next generation sequencing” adı verilmektedir. Bu karmaşık etkileşimlerin belirlenmesi için geliştirilen yeni teknikler ve biyoinformatik analiz programları sayesinde, erken tanıya yönelik biyobelirteçlerin bulunması ve bireysel tedavi yöntemlerinin geliştirilmesi mümkün olacaktır.Bu derlemede astımda etkili olan genlerin keşfinde kullanılan yeni ve eski teknikler  ve günümüzde astım genetiğende hangi noktada olduğumuz anlatılacaktır. Ayrıca elde edilen bilgilerin uygulamaya nasıl aktarılacağı ve gelecekte neler yapılması gerektiği tartışılacaktır.

Keywords

Astım, epigenetik, farmakogenetik, genetik

References

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