Determination of CYP2D6*3 and *4 allele frequency among Turkish population

Abstract

Aim: CYP2D6 takes part in the family of cytochrome P450 enzymes, which is account for the detoxification of multifarious xenobiotics and various drug commonly used in medicine. CYP2D6 is a polymorphic gene encompassing more than 80 known polymorphism within the coding and promoter regions. The mutant CYP2D6*3 allele revealed with the deletion of A2637 found in exon 5 region. The other common mutant allele is CYP2D6*4 and this allele stem from a splice site defect of G1934A can be classified as the most typical mutations. The present study primarily aims to determine the CYP2D6*3 and *4 frequency defects among Turkish population. 

Methods: Within the framework of the study, two critical alleles of CYP2D6 wild type allele, and CYP2D6*3 -CYP2D6*4 mutated alleles are genotyped on eighty healthy volunteers, who are unrelated, by the method of polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP).

Results: CYP2D6*4 allele frequency, which was identified as the loss of BstNI site, was determined as 13.16% on the examined reference group. Besides, the CYP2D6*4/CYP2D6*4 genotype ratio for the searched reference group was observed in only 2.63%. The heterozygous CYP2D6*3 allele frequency was determined as 1.32% on the examined reference group. Finally, CYP2D6*3/CYP2D6*3 genotype was not encountered in that searched reference group. 

Conclusion: In the light of those findings, it can be clearly stated that the prevalence of CYP2D6*3 and *4 allelic variants in the Turkish population is the same with the other demographic groups in Turkey. 

Keywords

• Xenobiotics,Turkish population,CYP2D6 polymorphism,PCR-RFLP

Türk popülasyonunda CYP2D6*3 ve *4 allel frekansının saptanması

Abstract

Amaç: CYP2D6, çeşitli ksenobiyotiklerin ve ilaçların detoksifikasyonundan sorumlu sitokrom P450 enzim ailesi içerisinde yer almaktadır. CYP2D6, kodlama ve promotör bölgelerinde 80'den fazla bilinen polimorfizm içeren bir polimorfik gendir. En tipik mutasyonlar olarak sınıflandırılan, CYP2D6*3 mutant alleli, ekson 5'de A2637’nin delesyonuyla, CYP2D6*4 mutant alleli ise G1934A'nın splice site defektiyle meydana gelmiştir. Bu çalışmada öncelikle Türk toplumunda CYP2D6*3 ve *4 frekans defektlerinin belirlenmesi amaçlanmıştır.

Yöntemler: Çalışma çerçevesinde; CYP2D6’nın iki kritik alleli olan wild tip ve mutant CYP2D6*3-*4 allelleri, birbirleriyle ilişkisiz 80 sağlıklı kontrol üzerinde, Polimeraz Zincir Reaksiyonu (PZR) ve Restriksiyon Fragment Uzunluk Polimorfizmi yoluyla genotiplendirilmiştir (RFLP). 

Bulgular: BstNI bölgesinin kaybı olarak tanımlanan CYP2D6*4 allel frekansı, incelenen referans grupta %13.16 olarak belirlenmiştir. Ayrıca; referans grupta araştırılan CYP2D6*4/CYP2D6*4 genotip oranının sadece %2.63 olduğu gözlemlenmiştir. Analiz edilen referans grupta; heterozigot CYP2D6*3 allel frekansı % 1.32 olarak tespit edilmiştir. Son olarak, CYP2D6*3/CYP2D6*3 genotipine araştırılan referans grubunda rastlanılmamıştır. 

Sonuç: Bu bulgular ışığında, Türk populasyonunda CYP2D6*3 ve *4 allelik varyant prevalanslarının diğer demografik gruplarla aynı olduğu açıkça belirtilebilir.

Keywords

• Zenobiyotik,Türk popülasyonu,CYP2D6 polimorfizmi,PZR-RFLP

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