Burçin KAYMAZ TEZCANLI, AYŞE ENDER ALTINTOPRAK, BÜLENT KAYAHAN, .Çağdaş AKTAN, Hakan COŞKUNOL, BUKET KOSOVA

Türk alkol bağımlılarında beyin kaynaklı nörotrofik faktör Val66Met polimorfizminin alkol bağımlılığına yatkınlık üzerine etkisinin araştırılması

Amaç: Multifaktöriyel ve poligenik kalıtım gösteren alkol bağımlılığının patofizyolojisinde, beyinde ifade edilen ve nöronal yaşam ile işlevsellikten sorumlu bir nörotrofin olan beyin kaynaklı nörotrofik faktör (BDNF) geni de rol almaktadır. Çalışmamızda, BDNF genindeki işlevsel Val66Met [G196A; (rs6265)] polimorfizminin Türk kadın ve erkek alkol bağımlısı olgulardaki yaygınlığının belirlenmesi ve bu polimorfizmin bağımlılığa yatkınlık üzerine etkisi- nin olup olmadığının belirlenmesi amaçlanmıştır. Yöntem: Çalışma ve kontrol gruplarını oluşturan 110 alkol bağımlısı olgu (10 kadın, 100 erkek) ve 376 sağlıklı bireyde (148 kadın, 228 erkek) BDNF Val66Met polimorfiz- minin genotip dağılımı ve alel sıklığı PZR-RFLP (Polimeraz Zincir Reaksiyonu-Restriksiyon Fragment Uzunluk Polimorfizmi) yöntemiyle belirlenmiş, istatistiksel analizler ki-kare ve ANOVA testleriyle gerçekleştirilmiştir. Bulgu- lar: Çalışma grubunu oluşturan olgular, kontrol grubu olgularıyla karşılaştırıldığında; mutant AA genotipinin dağılı- mı %3.6ya karşı %1.6 iken, A alelinin sıklığı %16.0a karşı %15.0 olarak belirlenmiştir. Bulgularımıza göre, çalış- ma grubu ve kontrol grubu, kadın olgular ile kadın kontroller ve erkek olgular ile erkek kontroller arasında genotip dağılımı ve alel sıklığı açısından anlamlı bir fark bulunmamaktadır. Çalışmanın gücü genotip analizi açısından %80.2 olarak hesaplanmıştır. Sonuç: Bu bulgular, BDNF geni polimorfik A alelinin Türk olgularda alkol bağımlılığıyla ilişkisinin olmadığını göstermektedir. Ancak AA genotipli erkek olguların alkol kullanmaya ve sorunlu içiciliğe başlama yaşının diğer genotiplere göre daha erken olduğunun belirlenmesi, alkol bağımlılığı fenotipinde BDNF polimorfizminin önemli olabileceğini düşündürmektedir.

Investigating the effect of brain derived neurotrophic factor Val66Met polymorphism upon alcoholism tendency in Turkish alcohol dependents

Objective: The neurotrophine brain derived neurotrophic factor (BDNF) which is expressed in the brain is re- sponsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to define the frequency of the functional Val66Met [G196A; (rs6265)] polymorphism of BDNF gene for Turkish male and female alcohol dependent cases and also to identify whether this polymorphism had any effect upon tendency to alcoholism. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method in 110 alcoholic cases (10 female, 100 male) and 376 healthy subjects (148 female, 228 male) constituting our study and control groups, statistical ana- lyses were revealed by chi-square and ANOVA tests. Results: The distribution of the mutant AA genotype was 3.6% to 1.6% and frequency of the A allele was 16.0% to 15.0% in the study group when compared to control group. Our results didnt show any significant differences in genotype distribution and allele frequencies of polymorphism neither between the study and control groups nor between female case and female controls and male alcoholics and male controls. The power of the study for genotype analysis was set at 80.2%. Conclusion: These results indicate that the polymorphic A allele of BDNF gene is not related with alcoholism in Turkish subjects. But since AA genotyped male subjects starting ages of alcohol usage and pathological drinking were detected to be earlier among other genotypes, this gave rise to a conclusion that BDNF polymorphism might be important in the alcoholism phenotype.

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