Varfarin tedavisi alan hastalarda CYP2C9 gen polimorfizminin araştırılması

Year 2020, Volume: 13 Issue: 3, 749 - 757, 18.09.2020

Tutku Erarslan İbrahim Türkçüer Aylin Köseler Ramazan Sabirli Atakan Yılmaz Mert Özen Abuzer Kekeç Fatih Çifçibaşı

https://doi.org/10.31362/patd.743452

Abstract

Amaç: Çalışmanın amacı warfarin tedavisi almakta olup hastanemize başvuran hastalarda, CYP2C9 gen polimorfizmi durumu ile haftalık doz ihtiyacı, INR düzeyleri arasında ilişkiyi incelemektir.
Gereç ve Yöntem: Pamukkale Üniversitesi Tıp Fakültesi Acil Servisine başvuran, warfarin tedavisi kullanan, toplam 100 hasta ve 100 kontrol grubu çalışma kapsamına alındı.
Bulgular: Warfarin kullanan grupta CYP2C9*1 allel frekansı 148(%74), CYP2C9*2 allel frekansı 17(%8,5), CYP2C9*3 allel frekansı 35(%17,5), CYP2C9*1/1 genotip frekansı 54 (%54), CYP2C9*1/2 genotip frekansı 11(%11), CYP2C9*1/3 genotip frekansı 29 (%29), CYP2C9*2/3 genotip frekansı 6(%6) olarak saptandı. Warfarin grubunun CYP2C9 genotiplerine ve allellere göre acil servis başvurusundaki INR düzeylerine bakıldığında genotipler veya alleller arasında INR düzeyi açısından istatistiksel anlamlı farklılık saptanmadı (Sırasıyla p=0,475 ve p=0,483). Warfarin kullanılmaya başlandıktan sonra ilk kontrolde yapılan INR ölçümlerinde wild tip genotipe veya allele sahip bireylerde INR düzeyi diğer genotip ve allellere sahip bireylere göre belirgin olarak daha düşük saptandı (Sırasıyla p=0,038 ve p=0,032). Warfarin tedavisi sırasında ölçülen pik INR değeri de aynı şekilde wild tip bireylerde diğer genotip veya allellere sahip bireylere göre daha düşük saptandı (Sırasıyla p=0,0001 ve p=0,008).
Sonuç: CYP2C9 geninin mutant allel veya genotiplerini taşıyan hastaların ilk ve pik INR değerlerinin mutasyonsuz olan gruba göre yüksek saptanmış olması bu allellerin warfarin metabolizmasına etkisini ortaya koymaktadır.

Keywords

CYP2C9 gen polimorfizmi, warfarin, antikoagülasyon

Supporting Institution

Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2016TIPF005

Investigation of CYP2C9 gene polymorphism in patients receiving warfarin therapy

Abstract

Purpose: The aim of the study is to investigate the relationship between CYP2C9 gene polymorphism status and weekly dose requirement and INR levels in patients who are receiving warfarin treatment and admitted to our hospital.
Materials and Methods: A total of 100 patients and 100 control groups who applied to the Emergency Department of Pamukkale University Medical Faculty, who used warfarin treatment were included in the study.
Results: CYP2C9*1 allele frequency 148 (74%), CYP2C9*2 allele frequency 17 (8.5%), CYP2C9*3 allele frequency 35 (17.5%), CYP2C9*1/1 genotype frequency 54 (%54), CYP2C9*1/2 genotype frequency 11 (11%), CYP2C9*1/3 genotype frequency 29 (29%), CYP2C9*2/3 genotype frequency 6 (6%) were found in the group using warfarin. When the warfarin group was measured according to CYP2C9 genotypes and alleles, there was no statistically significant difference between the genotypes or alleles in terms of INR levels (p=0.475 and p=0.483, respectively). In the INR measurements performed in the first control after the use of warfarin, the INR level was found to be significantly lower in individuals with wild type genotype or allele compared to individuals with other genotypes and alleles (p=0.038 and p=0.032 respectively). The peak INR value measured during warfarin treatment was likewise lower in wild-type individuals than in individuals with other genotypes or alleles (p=0.0001 and p=0.008, respectively).
Conclusion: The fact that the first and peak INR values of patients carrying the mutant allele or genotypes of the CYP2C9 gene were higher than the non-mutated group reveals the effect of these alleles on warfarin metabolism.

Keywords

CYP2C9 gene polymorphism, warfarin, anticoagulation

Project Number

2016TIPF005

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