Türk Popülasyonunda XRCC1 (Arg399Gln) ve XRCC3 (Thr241Met) Polimorfizmlerinin Genotip Dağılımı ve Allel Frekanslarının Belirlenmesi

Amaç: XRCC1 geni, serbest oksijen radikallerinin, iyonize radyasyonun, ultraviyole ve alkilleyici mutajenlerin yaptığı baz değişimi sonucu oluşan baz kesip çıkarma (eksizyon) onarımı ve DNA tek zincir kırılmalarının onarılmasında rol alan proteinleri kodlar. XRCC3 geni kimyasal ajanlar ve iyonize radyasyona karşı kromozomal bütünlük ve hücre direncini sağlayan çift zincir kırıkları, çapraz bağları ve homolog rekombinasyonda önemli bir rol oynamakta ve bu nedenle genomun stabilitesi için kritik önem taşımaktadır. Bu çalışmanın amacı Türk popülasyonunda XRCC1 (Arg399Gln) ve XRCC3 (Thr241Met) polimorfizmlerinin genotip dağılımı ve allel frekanslarının belirlenmesidir. Gereç ve Yöntem: Bu çalışmada Türk popülasyonunda XRCC1 (Arg399Gln) ve XRCC3 (Thr241Met) polimorfizmleri, polimeraz zincir reaksiyonu - restriksiyon parça uzunluğu polimorfizmi (PCR-RFLP) yöntemi kullanılarak araştırılmıştır. Bunun için aralarında akrabalık ilişkisi bulunmayan sağlıklı 260 gönüllüden alınan kan örnekleri kullanılmıştır. Bulgular: Çalışmamızın sonuçlarına göre XRCC1 (Arg399Gln) polimorfizmi için 104 (%40) bireyin Arg/Arg, 128 (%49,2) bireyin Arg/Gln ve 28 (%10,8) bireyin Gln/Gln genotipine sahip olduğu, Türk popülasyonunda Arg alel frekansının %64,6, Gln alel frekansının ise %35,4 olduğu tespit edilmiştir. XRCC3 (Thr241Met) polimorfizmi için ise 89 (%34,2) bireyin Thr/Thr, 122 (%46,9) bireyin Thr/Met, 49 (%18,9) bireyin Met/Met genotipine sahip olduğu, Türk toplumunda Thr ve Met alel frekanslarının sırasıyla %57,7 ve %42,3 olduğu tespit edilmiştir. Sonuç: Çalışmamız XRCC1 (Arg399Gln) polimorfizmi, sağlıklı Türk popülasyonunda yapılan örneklem büyüklüğü açısından en kapsamlı çalışmadır, ayrıca bu çalışma XRCC3 (Thr241Met) polimorfizminin sağlıklı Türk popülasyonunda dağılımının değerlendirildiği ilk çalışmadır. Bu sonuçlar klinikte bireye özgü tedavi yaklaşımlarının geliştirilmesini, çeşitli maruziyetlerde ve hastalıklarda Türk popülasyonunun vereceği cevabın değerlendirilerek riskli bireylerin belirlenmesini sağlayacaktır.

Determination of Genotype Distribution and Allele Frequencies of XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) Polymorphisms in Turkish Population

Objectives: XRCC1 gene encodes proteins which take part in base excision repair resulting from base exchanges made by free oxygen radicals, ionizing radiation, ultraviole and alkylating mutagens and in repair of DNA single-strand breaks. XRCC3 gene plays an important role in double strand breaks, crosslinks and homologous recombination which ensure chromosomal integrity and cell resistance against chemical agents and ionizing radiation, and is therefore critical for the stability of the genome. The purpose is to determine genotype type and allele frequencies of XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms in Turkish population. Materials and Methods: In this study, the polymorphism of XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) was investigated using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method in the Turkish population. For this, blood samples were used from 260 healthy volunteers with no consanguinity. Results: According to the results of our study, for the XRCC1 (Arg399Gln) polymorphism, 104 (40%) individuals had Arg/Arg, 128 (49.2%) individuals had Arg/Gln and 28 (10.8%) individuals had Gln/Gln genotype; in the Turkish population, the frequency of Arg allele was determined as 64.6% and the allele frequency was to be 35.4%. For the XRCC3 (Thr241Met) polymorphism, 89 (34.2%) individuals had Thr/Thr, 122 (46.9%) individuals had Thr/Met, 49 (18.9%) individuals had Met/Met genotype; and in Turkish population, Thr and Met allele frequencies were found to be 57.7% and 42.3%, respectively. Conclusion: Our study is the most comprehensive study about XRCC1 (Arg399Gln) polymorphism in terms of sample size of healthy Turkish population, and this is the first study to evaluate the distribution of XRCC3 (Thr241Met) polymorphism in the healthy Turkish population. These results will enable the development of individual-specific treatment approaches in the clinic, and the identification of risky individuals by evaluating the response of the Turkish population in various exposures and diseases.

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