Sigara Bağımlılığının Genetiği

Öz

Tobacco smoking is associated with many diseases causing 5 million deaths per year worldwide and is regarded as one of the leading causes of death. Addiction is of the most notorious tobacco-related syndrome and is mainly attributed to nicotine. The causes of tobacco smoking addiction were intensively investigated with several components. Epidemiologic, pharmacologic, neurobiological and genetic studies were main study topics. Genetic studies of smoking and nicotine dependence has been studied for 50 years. Twin, family and adoption studies show evidence for genetic effects on smoking and nicotine dependence. Molecular genetic analyses have identified genes associated with the amount smoked and nicotine dependence. The high heritability of addiction has stimulated much work aimed at identifying susceptibility genes using positional genetics. Candidate gene approaches are also being used for the genetic dissection of smoking addiction. These two approaches had a major impact on our understanding of disease pathophysiology in last 2 decades. Recent work indicates that epigenetic mechanisms or the chemical markings of the DNA and the surrounding histone proteins remain labile through the lifespan and can be altered by environmental factors. Thus, epigenetic mechanisms are an attractive molecular hypothesis for environmental contributions to tobacco smoking addiction. Genome wide association and copy number variation studies are new genetic techniques and they would probably provide us important information in the near future. In this report we aimed to review progress of genetic studies in smoking addiction from classical genetic studies to new epigenetic approaches.

Anahtar Kelimeler

• Smoking, addiction, genetics, epigenetics

Genetics of Smoking Addiction

Öz

Sigara birçok hastalığın sebepleri arasındadır ve her yıl 5 milyon insanın ölümüne neden olarak, en önemli ölüm nedenleri arasında yer almaktadır. Bağımlılık, sigara kullanımının yol açtığı en önemli sendromlardandır ve içerdiği nikotin ile ilişkilendirilmiştir. Sigara bağımlılığının nedenleri farklı bileşenleri ile yoğun bir şekilde araştırılmıştır. Epidemiyolojik, farmakolojik, nörobiyolojik ve genetik çalışmalar başlıca çalışma alanlarıdır. Sigara ve nikotin bağımlılığının genetiği 50 yıldır çalışılmaktadır. Öncelikle, İkiz, aile ve evlat edinme çalışmaları sigara bağımlılığında genetik geçişin olduğunu göstermiştir. Moleküler genetik çalışmalar ile, içilen sigara miktarı ve nikotin ile aday genler arasında ilişkili olduğu gösterilmiştir. Bağımlılığın yüksek derecede kalıtsal bir hastalık olması, pozisyonel genetiği kullanarak şüphelenilen genlerin aydınlatılmasına çalışılması için birçok çalışmanın yapılmasını tetiklemiştir. Sigara bağımlılığı genetik diseksiyonu için aday gen çalışmaları da ayrıca kullanılmaktadır. Bu iki yaklaşımın son 20 yılda hastalık patofizyolojisini anlamamızda önemli etkisi olmuştur. Sigara bağımlılığında tüm genomun incelendiği ilişkilendirme çalışmaları ve kopya sayısı değişikliklerinin tespiti de yakın gelecekte önemli katkı sağlayabilecektir. Yeni çalışmalar, epigenetik mekanizmaların veya DNA'nın kimyasal belirteçlerinin ve onu çevreleyen histon proteinlerinin yaşam boyu değişken olduğunu ve çevresel faktörler tarafından değiştirilebileceğini göstermiştir. Epigenetik mekanizmalar, çevresel koşulların şizofreniye etkisini açıklayan cazip bir moleküler hipotez olmuştur. Bu yazıda, klasik genetik çalışmalardan yeni epigenetik yaklaşımlara kadar sigara bağımlılığındaki genetik çalışmaların gelişimini gözden geçirilmiştir.

Anahtar Kelimeler

• Sigara, bağımlılık, genetik, epigenetik

Kaynakça

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