Türkiye Popülasyonunda UGT1A4 ve UGT1A6 Genetik Profillerinin Değerlendirilmesi

Öz

Amaç: Üridin difosfat glukuronosiltransferazlar (UGT'ler), konjugasyon faz II enzimlerinin bir süper ailesidir ve birçok endobiyotik veya ksenobiyotik substratın glukuronidasyonunu katalize etmekten sorumludur. Bu çalışmada, sağlıklı Türk popülasyonunda UGT1A4 c.142T>G, UGT1A6 c.541A>G ve UGT1A6 c.19T>G polimorfizmlerinin allel ve genotip frekanslarının belirlenmesi ve farklı popülasyon verileriyle karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: UGT1A4 c.142T>G, UGT1A6 c.541A>G ve c.19T>G polimorfizmleri, polimeraz zincir reaksiyonu ve restriksiyon fragman uzunluğu polimorfizmi yöntemleri kullanılarak 114 sağlıklı Türk gönüllülerinin DNA örneklerinde belirlendi. Bulgular: Varyant allel frekansları UGT1A4 c.142T>G için % 12.7, UGT1A6 c.541A>G için % 39.9 ve UGT1A6 c.19T>G için % 44.7 idi. Belirlenen UGT1A4 ve UGT1A6 varyant allel frekanslarının, Avrupa popülasyonlarının çoğunluğuna benzer olduğu gözlendi. Ancak, Türk popülasyonundaki UGT1A6 frekanslarının, özellikle Tayland ve Doğu Asya popülasyonlarının frekanslarından önemli ölçüde farklıydı. Sonuç: Bu çalışma, Türk popülasyonunda UGT1A4 ve UGT1A6 polimorfizmlerinin sıklığını sunmaktadır. Bildiğimiz kadarıyla, sağlıklı bir Türk popülasyonunda UGT1A6 c.541A>G ve c.19T>G polimorfizmlerinin sıklığını araştıran ilk rapordur. Literatür taramasında Türk epilepsi hastalarında UGTA1A4*3 polimorfizmi ile ilgili bir çalışma bulundu, ancak sağlıklı bireyler ile ilgili veri bulunmadı. Dolayısıyla bu çalışmanın, sağlıklı Türk bireylerinde UGT1A4*3 polimorfizmini araştıran ilk rapor olduğu ifade edilebilir. Bu çalışma, Türk popülasyonunda UGT1A4 ve UGT1A6 ile gerçekleşen ilaç metabolizması hakkında klinik olarak faydalı bilgiler sağlayabilir.

Anahtar Kelimeler

• UGT1A4
• UGT1A6
• glukuronidasyon
• polimorfizm
• Türk popülasyonu

The Evaluation of Genetic Profiles of UGT1A4 and UGT1A6 in the Turkish Population

Öz

Aim: Uridine diphosphate glucuronosyltransferases (UGTs) are a superfamily of conjugation phase II enzymes and is responsible for catalyzing the glucuronidation of many endobiotic or xenobiotic substrates. The present study aimed to determine allele and genotype frequencies of UGT1A4 c.142T>G, UGT1A6 c.541A>G and UGT1A6 c.19T>G polymorphisms in the healthy Turkish population and also to compare them with different population data. Material and Method: UGT1A4 c.142T>G, UGT1A6 c.541A>G and c.19T>G polymorphisms were determined in DNA samples of 114 healthy Turkish volunteers using polymerase chain reaction and restriction fragment length polymorphism methods. Results: The frequencies of variant alleles were 12.7% for UGT1A4 c.142T>G, 39.9% for UGT1A6 c.541A>G and 44.7% for UGT1A6 c.19T>G. The frequencies of the UGT1A4 and UGT1A6 variant alleles determined were observed to be similar to those of the majority of European populations. However, the UGT1A6 frequencies in the Turk population differed significantly from those reported specifically for the Thai and East Asian populations. Conclusion: This study introduces the frequencies of UGT1A4 and UGT1A6 polymorphisms in the Turkish population. To our knowledge, this is the first report that investigated the frequencies of UGT1A6 c.541A>G and c.19T>G polymorphisms in a healthy Turkish population. A study of the UGTA1A4*3 polymorphism was found in Turkish epilepsy patients in the literature search, but not in healthy individuals. Therefore, it can be stated that this study is also the first report investigating the UGT1A4*3 polymorphism in the healthy Turkish individuals. This study could ensure clinically beneficial information about drug metabolism by UGT1A4 and UGT1A6 in Turkish population.

Anahtar Kelimeler

• UGT1A4
• UGT1A6
• glucuronidation
• polymorphism
• Turkish population

Kaynakça

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