Mehmet Emin ERDAL, Tolgay ERGENOĞLU, Hüseyin BEYDAĞI, Tamer DEMİRALP, Gonca COŞKUN, H. Yasemin KESKİN

Triptofan hidroksilaz gen polimorfizminin işitsel olaya ilişkin beyin potansiyellerine etkisi

Triptofan hidroksilaz enzimi ile triptofandan sentezlenen serotonin (5-HT) merkezi sinir sisteminde önemli bir nörotransmiterdir. Triptofan hidroksilaz (TPH), serotonin sentezinin başlangıç ve hız kısıtlayıcı basamağıdır. Bu çalışmada, TPH geninin 7. intronundaki adeninsitozin dönüşümü sonucu ortaya çıkan A218C polimorfizminin işitsel olaya ilişkin potansiyeller (OİP) üzerine etkisi olup olmadığı araştırılmıştır. Bu amaçla 48 sağlıklı erkek gönüllüde işitsel oddball ve yenilik (novelty) paradigması uygulanarak OİP'ler kaydedilmiştir. Denekler A218C polimorfizmi açısından üç genotip grubuna ayrılmışlardır. Elde edilen OİP dalgalarının genlik ve latansları ölçülerek gruplar arasındaki farklar ANOVA testiyle analiz edilmiş, A218C polimorfizmine göre C/C genotipli grupta oddball paradigmasındaki hedef uyaranlara karşı P200 yanıtlarının latansının A/C genotipli gruba göre daha uzun olduğu saptanmıştır (p=0.007). C/C ve A/C genotipli gruplar arasında üç uyaran paradigmasındaki hedef uyaranlar için de istatistiksel olarak trend düzeyinde bir latans farkı saptanmıştır (p=0.079). Sonuçlarımız serotonerjik aktivitede TPH gen polimorfizmine bağlı olarak oluşan değişimlerin işitsel OİP'lerin önemli bir bileşeni olan P200 latansını etkilediğini göstermektedir.

The effect of tryptophan hydroxylase gene polymorphism on auditory event related brain potentials

Background and Design.- Serotonin (5-HT) which is synthesized from tryptophan with tryptophan hydroxylase enzyme is an important neurotransmitter in the central nervous system. Tryptophan hydroxylase (TPH) is the initial step and rate-limiting enzyme in the synthesis of serotonin. Present study investigated whether A218C polymorphism on the seventh intron that is caused by adenin-cytosine transition of TPH gene has an effect on auditory event-related potentials (ERP). Forty-eight healthy male volunteers participated in this study. N100, P200 and P300 potentials elicited with auditory oddball and novelty paradigms. Subjects were grouped according to the A218C polymorphism of TPH gene identified using the PCR method. The differences in amplitude, latency and topographic distribution of ERPs between the genotype groups were tested with repeated measures ANOVA. Results.- The latency of the P200 in response to the oddball targets was longer in C/C genotype than in the A/C genotype group (p=0.007). There was also a trend for longer P200 latencies obtained with the novel stimuli of the novelty paradigm for the C/C group (p=0.079). Conclusion.- Our results suggest that differentiation in serotonergic activity that results from TPH gene polymorphism may alter auditory ERPs.

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