Amaç: Bu çalışmada, CYP2C9 ve CYP2C19 genlerin kopya sayısı varyasyon (CNV) ile klopidogrel direnç mekanizması arasındaki ilişkinin araştırılması amaçlanmıştır. Yöntem: Çalışmaya, acil veya elektif stent implantasyonlu perkütan koroner girişim uygulanan 176 hasta dahil edildi. 600 mg klopidogrel yükleme dozu alan ve en az 5 gün süreyle standart doz (75 mg/gün) klopidogrel kullanan hastalardan alınan kan örneklerinde PFA-100 P2Y12 kiti ile kapanma zamanı ölçüldü. Hastalar kapanma zamanı değeri >106 saniye olanlar klopidogrele dirençli, ≤106 saniye olanlar klopidogrele dirençli olmayan olarak iki gruba ayrıldı. Hastalardan alınan tam kan örneklerinden Purelink Genomic DNA izolasyon kiti kullanılarak DNA izole edildi. CYP2C9 ve CYP2C19 genlerin kopya sayısı varyasyonları TaqMan kopya sayısı analiz kiti kullanılarak RT-PCR ile tespit edildi. Bulgular: Çalışmamızda %55.11 bireyde klopidogrel direnci yok iken, %44.89 bireyde ise klopidogrel direncine sahip olduğu saptadık. ). CYP2C19 (Hs05107177-intron 8) iki kopyaya sahip bireylerin bir ve üç kopyaya sahip bireylere göre sırası ile 4.91 ve 3,57 kat daha fazla klopidogrel ilaç̧ direnci geliştirme riskine sahip olduğu belirlendi. Sonuç: Elde ettiğimiz verilere göre, CYP2C19 (Hs05107177- intron 8) kopya sayısı varyasyonlarına sahip bireylerin klopidogrel direnci gelişme riskinin daha yüksek olduğunu göstermektedir.
Aim: This study aimed to investigate the relationship between copy number variation (CNV) of CYP2C9 and CYP2C19 genes and the clopidogrel resistance mechanism. Method The study included 176 patients who underwent emergency or elective percutaneous coronary intervention with stent implantation. Closure time was measured with PFA-100 P2Y12 in blood samples taken from patients using clopidogrel with a standard dose (75 mg/day) for at least 5 days after 600 mg clopidogrel loading dose. The patients were divided into two groups closure time values >106 s as resistant to clopidogrel, ≤106 s were nonresistant to clopidogrel. DNA was isolated from whole blood samples taken from patients using the Purelink Genomic DNA isolation kit. CNVs of CYP2C9 and CYP2C19 genes were detected by RT-PCR using the TaqMan copy number assay kit. Results: In our study, we found that 55.11% of individuals did not have clopidogrel resistance, while 44.89% of individuals had clopidogrel resistance. In this study, it was shown that there was no statistically significant difference between CYP2C9 (Hs0518754), CYP2C9 (Hs05165291), CYP2C9 (Hs05165291), CYP2C19 (Hs02932336) and CYP2C19 (Hs05148033) CNVs and clopidogrel resistance (p˃0.05). It was determined that individuals with the two copies of CYP2C19 (Hs05107177-8 intron) have a 4.91- and 3.57-fold increased risk of developing clopidogrel drug resistance compared to the one and three copy, respectively. Conclusion: Our data show that individuals with CYP2C19 (Hs05107177- intron 8) copy number variations have a higher risk of developing clopidogrel resistance.
Primary Language | Turkish |
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Subjects | Medical Pharmacology, Pharmacology and Pharmaceutical Sciences (Other) |
Journal Section | Articles |
Authors | |
Early Pub Date | August 2, 2024 |
Publication Date | August 16, 2024 |
Submission Date | November 17, 2023 |
Acceptance Date | January 16, 2024 |
Published in Issue | Year 2024 Volume: 17 Issue: 2 |
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
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