Timidilat Sentaz 2T Gen Polimorfizmi Akut Lösemi İçin Bir Risk Faktörüdür
DOI: 10.26650/experimed.2018.18005Amaç: Folat metabolizması içerisinde yer alan timidilat sentaz (TS) enzimi, deoksiüridin monofosfatın (dUMP), deoksitimidin monofosfata (dTMP) dönüşümünü katalizlemektedir. Hücre içerisinde DNA sentezi için gerekli olan deoksinükleotidlerin belirli bir denge de bulunmasını sağlamaktadır. Enzimin inhibisyonu sonucu anormal kromozom kırıklarının oluştuğu ve hücre ölümünün gerçekleştiği gösterilmiştir. Çoğalan hücreler için çok gerekli olan enzim aynı zaman da değişik kanser ilaçlarına da hedef olmaktadır. Kromozom 18p11.32 de bulunan TS geni, ATG başlama bölgesinin hemen üzerinde polimorfik tekrar bölgesi içermektedir. 28 bazlık tekrar dizisinin ikili veya üçlü tekrarından oluşan bu polimorfizmin, in vitro ve in vivo olarak gen ekspresyonunda farklılık oluşturduğu gösterilmiştir. Benzeri çalışmalar ile pek çok kanser türü ve kanser ilacı kullanımı ile TS polimorfizmi ilişkisi sorgulanmıştır. Bu çalışmada Türk populasyonunda akut lösemi etiyolojisinde (Akut myeloid lösemi ve Akut lenfoblastik lösemi) TS promoter polimorfizminin rolünün araştırılması amaçlanmıştır. Yöntemler: Çocukluk çağı akut lenfoblastik lösemi (ALL) (n=110) ve çocukluk çağı ve erişkin akut myeloid lösemi (AML) (n=126) olgularından elde edilen DNA’larla bölgeye özgü primerler kullanılarak yapılan PZR sonrası agoroz jel elektroforezi analizi ile iki veya üç tekrardan oluşan TS polimorfik allelleri belirlendi. Sonuçlar sağlıklı kontrol (n=133) olgularının sonuçları ile karşılaştırarak istatistiksel olarak TS gen polimorfizminin bir risk oluşturup oluşturmadığını sorgulandı. İstatistiksel analizler, SPSS programındaki Fisher’s exact test kullanılarak yapıldı. Bulgular: AML olgularında TS promoter polimorfizmi ile ilişki bulunmadı. Çocukluk çağı ALL olgularında 2T/2T genotipi anlamlı düzeyde yüksek bulundu (p=0,048). Sonuç: Çalışmamız ALL gelişiminde, 2T/2T genotipinin bir risk faktörü olduğunu fakat diğer genotiplerin ALL ve AML oluşumunda bir risk oluşturmadığını göstermiştir.
Anahtar Kelimeler:
Akut lösemi, polimorfizm, timidilat sentaz
Thymidylate Synthase 2T Gene Polymorphism is a Risk Factor for Acute Leukemia
DOI: 10.26650/experimed.2018.18005Objective: The enzyme thymidylate synthase (TS) in the folate metabolism catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). It provides a certain balance of deoxynucleotides required for DNA synthesis in the cell. Inhibition of the enzyme showed that abnormal chromosomal breakage and apoptosis occurred. The enzyme, which is necessary for proliferating cells, also targeted different cancer drugs. The TS gene at chromosome 18p11.32 contains the polymorphic repeat region just upstream of the ATG starting site. This polymorphism, consisting of double or triple repeats of the 28-base length sequence, has been shown to differ in gene expression in vitro and in vivo. Similar studies have investigated the relationship between many types of cancer and cancer drug use and TS polymorphism. In this study, the role of TS promoter polymorphism in acute leukemia etiology (acute myeloid leukemia and acute lymphoblastic leukemia) in the Turkish population was investigated.Material and Method: For this purpose, a pediatric acute lymphoblastic leukemia (ALL) case admitted to our unit (n=110) and agorose gel electrophoresis after PCR using region-specific primers with DNA obtained from pediatric and adult acute myeloid leukemia (AML) (n=126) TS polymorphic alleles consisting of two or three repetitions were determined. The results were compared with the results of healthy control (n=133) cases, and we questioned whether TS gene polymorphism is a risk factor.Results: Statistical analyses were performed using the Fisher exact test in the program SPSS, and the 2T/2T genotype was a risk factor in the formation of ALL (p=0.048). Conclusion: It was observed that other genotypes did not have a risk for ALL and AML formations.
Keywords:
Acute leukemia, polymorphism, thymidylate synthase,
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- Yayın Aralığı: Yılda 3 Sayı
- Başlangıç: 2011
- Yayıncı: İstanbul Üniversitesi
Sayıdaki Diğer Makaleler
X. AZİZ SANCAR DETAE GÜNLERİ İmmün Sistem Yetersizlikleri ve Aşılar 29-30 Kasım 2018
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