Yüksek Doz Metotreksat Alan Akut Lenfoblastik Lösemili Çocuklarda, AANAT Gen Polimorfizmi ve Gen Ekspresyon Düzeyinin Araştırılması
Küçük Resim Yok
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Melatonin uyku, sirkadiyan ritim, adrenal bez ve tiroit bezi fonksiyonları, üreme, yaşlanma, antioksidan sistem ve bağışıklık gibi birçok biyolojik fonksiyonun düzenlenmesinde rol oynar. Metotreksat 5 g/m²/24 saat infüzyon tedavisi alan Akut Lenfoblastik Lösemili çocuklarda Metotreksat’ın; melatonin seviyesi üzerindeki etkisinin ve melatonin biyosentezinde görev alan AANAT kodlayan genin promotor bölgesinde yer alan -263 G/C değişiminin ve gende belirlenecek diğer olası değişimlerin saptanması bu değişimlerin; AANAT gen ifadelenmesi üzerindeki etkisinin incelenmesidir. Gereçler ve Yöntem: Çalışmaya Lösante Çocuk ve Yetişkin hastanesinde 16 akut lenfoblastik lösemi tanısı almış çocuk hasta dâhil edildi. İlk aşamada olgulardan elde edilen DNA örneklerinde AANAT geni -263 G/C değişimi dizi analizi yöntemi ile incelendi. 5 g/m²/24 saat metotreksat infüzyon öncesi ve sonrası hastalardan RNA izolasyonu yapıldı ve elde edilen RNA örneklerinden Kantitatif Real Time yöntemi ile AANAT geni ifade düzeyleri belirlendi. Bulgular: AANAT geni dizi analizi sonuçlarında -263 G/C promotor bölge değişimi noktasında 3 hasta Homozigot mutant, 12 hasta Heterozigot ve 1 hastada yabanıl genotipe sahip olduğu belirlenmiştir. AANAT gen ifadesinin 5 g/m²/24 saat metotreksat infüzyonu öncesi ve sonrası farklı olduğu belirlenmiştir. Sonuç: Serotonin’in Melatonin’e dönüştürülmesinde rol oynayan AANAT enzimi lösemi tedavisinde kullanılan Metotreksat infüzyonundan etkilenmiştir. Bu çalışmanın hasta sayısı artırılarak ve melatonin sentez mekanizmasında görev alan diğer genler ile birlikte çalışması ve aydınlatılması planlanmıştır.
Objective: Melatonin has a role in regulation of many physiological processes such as sleep, circadian rhythm, functions of adrenal and thyroid gland, reproduction, aging, antioxidant system, and immunity. In this study, we aimed to analyze the frequency of -263 C/G polymorphism localized in promoter region of the gene coding AANAT enzyme and its effect to the expression of AANAT gene in pediatric Acute Lymphoblastic Leukemia patients receiving high dose Methotrexate (5 g/m²/d). Material and Methods: Study population consisted of 16 who were admitted to Losante Children and Adult hospital with the diagnosis of Acute Lymphoblastic Leukemia. Amplification of gene was performed by Polymerase chain reaction and DNA sequencing by sequencer. For RNA isolations, blood samples were collected from patients group before and after therapy. Expression analysis was performed with the relative basic quantification software comes with quantitive Real Time Polymerase chain reaction. Results: In the results of AANAT sequencing, 3 homozygous mutants, 12 heterozygotes and 1 patient wild genotype were determined at -263 G / C promoter region. The AANAT gene expression was determined to be different before and after methotrexate infusion of 5 g / m² / 24 h. Conclusion: The AANAT enzyme which plays a role in converting serotonin to melatonin has been influenced by the methotrexate infusion used in the treatment of leukemia. Further research will be required to determine the genetic bases of melatonin mechanism.
Objective: Melatonin has a role in regulation of many physiological processes such as sleep, circadian rhythm, functions of adrenal and thyroid gland, reproduction, aging, antioxidant system, and immunity. In this study, we aimed to analyze the frequency of -263 C/G polymorphism localized in promoter region of the gene coding AANAT enzyme and its effect to the expression of AANAT gene in pediatric Acute Lymphoblastic Leukemia patients receiving high dose Methotrexate (5 g/m²/d). Material and Methods: Study population consisted of 16 who were admitted to Losante Children and Adult hospital with the diagnosis of Acute Lymphoblastic Leukemia. Amplification of gene was performed by Polymerase chain reaction and DNA sequencing by sequencer. For RNA isolations, blood samples were collected from patients group before and after therapy. Expression analysis was performed with the relative basic quantification software comes with quantitive Real Time Polymerase chain reaction. Results: In the results of AANAT sequencing, 3 homozygous mutants, 12 heterozygotes and 1 patient wild genotype were determined at -263 G / C promoter region. The AANAT gene expression was determined to be different before and after methotrexate infusion of 5 g / m² / 24 h. Conclusion: The AANAT enzyme which plays a role in converting serotonin to melatonin has been influenced by the methotrexate infusion used in the treatment of leukemia. Further research will be required to determine the genetic bases of melatonin mechanism.
Açıklama
Anahtar Kelimeler
Cerrahi
Kaynak
Zeynep Kamil Tıp Bülteni
WoS Q Değeri
Scopus Q Değeri
Cilt
49
Sayı
4
