İki uçlu bozukluk hastalarında lityuma yanıt ile GSK-3? polimorfizmi ilişkisinin değerlendirilmesi
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Dosyalar
Tarih
2018
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Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: İki uçlu bozukluk tedavisinde köşe taşı seçenek olan lityuma, tedavi yanıtını gösteren klinik öngörücülerin kanıt düzeyi yetersizdir. Lityumun etki düzeneğini araştıran çalışmalar glikojen sentaz kinaz 3 beta (GSK-3?) enzimi inhibisyonunun tedavide de önemli olduğunu göstermektedir. Buradan hareketle lityum tedavi yanıtı ile GSK-3? beş farklı polimorfizmi arasındaki ilişkiyi incelemeyi amaçladık.Yöntem: İki uçlu Bozukluk tip 1 tanısı almış ardışık 100 hastaya ait has-tane tıbbi kayıtları incelenerek Lityum Tedavi Yanıt Ölçeği (LTYÖ) pu-anları hesaplanmıştır. Hastaların tıbbi kayıtları ve hastalık seyirleri klinik görüşme ile teyit edildi. Kan örnekleri EDTA’lı tüpe alındı ve MagNA Pure Compact otomatik izolasyon yöntemi ile genomik DNA elde edildi. GSK-3? rs17183904, rs17183897, rs34009575, rs34002644, rs17183890 polimorfizmleri Real Time PCR tecnic LightCycler 2,0 (Roche) ile analiz edildi.Bulgular: Hastaların ortalama yaşı 41,110,3 yıl, hastalık başlangıç yaşı 24,58,2 ve LTYÖ puanları ise 4,91,8 puan olarak bulundu. Hastala-rın LTYÖ puanları karşılaştırıldığında cinsiyet, medeni durum, öğre-nim durumu, ilk hastalık dönemi türü açısından anlamlı fark saptanma-dı. GSK-3? rs17183890 AG genotipinde lityuma tedavi yanıt puanları daha yüksek olarak bulunurken (p0,008, t:2,71) diğer polimorfizmler-de anlamlı farklılık saptanmadı.Sonuç: Araştırmamızda saptadığımız GSK-3? özgül polimorfizminin bireyselleşmiş tedavilerin geliştirmesine olanak sağlayarak yan etkiler ve tedavi uyumu açısından klinik pratiğe önemli katkı sağlayacağını dü-şünmekteyiz. Bunun için daha geniş örneklemi içeren genom boyu tara-ma çalışmalarına ihtiyaç vardır.
Objective: There is a lack of evidence regarding clinical predictors for the treatment response to lithium, which is the main stay treatment option for bipolar disorder. Studies that examined the mechanistic action of lithium revealed that glycogen synthase kinase 3? (GSK-3?) enzyme-inhibition was important in regard to treatment responses. Based on this background, we aimed to investigate the association between responses to lithium treatment and five different polymorphisms of GSK-3?.Method: Lithium treatment response scale (LTRS) scores for 100 patients diagnosed with bipolar disorders type I were calculated according to the hospital records. Blood samples were collected and genomic DNA was obtained using the MagNA Pure Compact automatic isolation method. The GSK-3?: rs17183904, rs17183897, rs34009575, rs34002644, and rs17183890 polymorphisms were analyzed by real time PCR.Results: In this cohort, the mean age of patients was 41.110.3 years, the mean age of disease onset was 24.58.2, and the mean LTRS score was 4.91.8. There was no statistically significant difference for LTRS scores between groups in terms of gender, marital status, level of education, and the type of first episode. LTRS was significantly higher in only the patients harbouring GSK-3? rs17183890 AG genotype (p0.008, t:2.71). Interestingly, no differences were found for the remaining polymorphisms.Conclusion: The specific GSK-3? polymorphism that associated with lithium-response in our study may help to predict lithium responses and to develop individualized treatment. We presume that our pharmacogenomic findings may also provide important contributions to the clinical practice in regard to future evaluation of the treatment adherence and side effects. To obtain these goals, further genome-wide scanning studies conducted on larger sample cohorts are required.
Objective: There is a lack of evidence regarding clinical predictors for the treatment response to lithium, which is the main stay treatment option for bipolar disorder. Studies that examined the mechanistic action of lithium revealed that glycogen synthase kinase 3? (GSK-3?) enzyme-inhibition was important in regard to treatment responses. Based on this background, we aimed to investigate the association between responses to lithium treatment and five different polymorphisms of GSK-3?.Method: Lithium treatment response scale (LTRS) scores for 100 patients diagnosed with bipolar disorders type I were calculated according to the hospital records. Blood samples were collected and genomic DNA was obtained using the MagNA Pure Compact automatic isolation method. The GSK-3?: rs17183904, rs17183897, rs34009575, rs34002644, and rs17183890 polymorphisms were analyzed by real time PCR.Results: In this cohort, the mean age of patients was 41.110.3 years, the mean age of disease onset was 24.58.2, and the mean LTRS score was 4.91.8. There was no statistically significant difference for LTRS scores between groups in terms of gender, marital status, level of education, and the type of first episode. LTRS was significantly higher in only the patients harbouring GSK-3? rs17183890 AG genotype (p0.008, t:2.71). Interestingly, no differences were found for the remaining polymorphisms.Conclusion: The specific GSK-3? polymorphism that associated with lithium-response in our study may help to predict lithium responses and to develop individualized treatment. We presume that our pharmacogenomic findings may also provide important contributions to the clinical practice in regard to future evaluation of the treatment adherence and side effects. To obtain these goals, further genome-wide scanning studies conducted on larger sample cohorts are required.
Açıklama
Anahtar Kelimeler
Psikiyatri, Psikoloji
Kaynak
Türk Psikiyatri Dergisi
WoS Q Değeri
Scopus Q Değeri
Cilt
29
Sayı
2
Künye
Altınbaş, K., Yeşilbaş, D., İnce, B., Cansız, A., Sılan, F., Özdemir, Ö., Gülöksüz, S. (2018). İki Uçlu Bozukluk Hastalarında Lityuma Yanıt ile GSK-3β
Polimorfizmi İlişkisinin Değerlendirilmesi. Türk Psikiyatri Dergisi, 29(2), 73-78.
