The relationship of CYP2C9 and CYP2C19 gene copy number variations with clopidogrel resistance after percutaneous coronary intervention

Öz

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.

Anahtar Kelimeler

• Copy number variation
• CYP
• clopidogrel resistance
• cutaneous coronary intervention

Perkütan koroner gı̇rı̇şı̇m sonrası klopı̇dogrel dı̇rencı̇nı̇n CYP2C9 ve CYP2C19 genlerı̇nı̇n kopya sayısı varyasyonu ile ı̇lı̇şkı̇sı̇

Öz

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.

Anahtar Kelimeler

• Kopya sayısı varyasyon
• CYP
• klopidogrel direnci
• perkütan koroner girişim

Kaynakça

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