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"Latar Belakang. Clopidogrel adalah salah satu pilihan antiplatelet pada kasus stroke iskemik yang bekerja dengan menghambat ikatan adenosine diphosphate (ADP) dengan reseptor P2Y12. Gen ABCB1 diketahui mengkode transporter P-glikoprotein (P-gp) multidrug resistance-1 (MDR1) yang mempengaruhi absorpsi clopidogrel di usus, sehingga mempengaruhi efektivitasnya dalam mencegah agregasi trombosit. Penelitian ini bertujuan untuk menilai peran polimorfisme gen ABCB1 terhadap variabilitas respons clopidogrel yang dilihat dari agregasi trombosit serta mengetahui frekuensi genotip ABCB1 pada populasi.Metode. Studi potong lintang dilakukan pada pasien stroke iskemik yang mengkonsumsi clopidogrel di RSUI/RSCM pada 2020-2023. Dilakukan pemeriksaan polimorfisme ABCB1 C3435T dan C1236T serta agregasi trombosit dengan VerifyNow PRU. Variabilitas respons clopidogrel dikelompokkan menjadi tidak respons (>208 PRU), respons (95-208 PRU), dan risiko perdarahan (<95 PRU).Hasil. Sebanyak 124 subjek direkrut dalam penelitian, dengan 12,9% subjek tidak respons, 45,9% respons, dan 41,9% lainnya memiliki risiko perdarahan terhadap pemberian clopidogrel. Genotip homozigot wildtype (CC) pada ABCB1 C1236T memiliki kemungkinan risiko perdarahan pada konsumsi clopidogrel 3,76 kali lebih tinggi (p=0,008; 95%CI 1,41-10,07) dibandingkan varian lainnya (CT/TT). Frekuensi genotip ABCB1 C3435T subjek pada kelompok homozigot wildtype, heterozigot, dan homozigot varian berturut-turut sebesar 35,9%, 43,5% dan 16,9%. Sementara itu, pada genotip C1236T berturut-turut sebesar 17,8%, 39,5%, dan 42,7%.Kesimpulan. Genotip ABCB1 C1236T varian homozigot wildtype memiliki kemungkinan risiko perdarahan 3,76 kali lebih tinggi pada pemberian clopidogrel. Frekuensi genotip terbanyak pada ABCB1 C1236T adalah homozigot varian, sementara pada ABCB1 C3435T adalah heterozigot.

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Background. Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency.

Methods. A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020-2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (>208 PRU), responsive (95-208 PRU), and bleeding risk (<95 PRU).

Results. 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p=0,008; 95%CI 1,41-10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively.

Conclusion. ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

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"Leukemia granulositik kronik (LGK) merupakan salah satu penyakit keganasan hematologi yang prevalensinya dapatterus meningkat di masa depan. Terapi LGK saat ini adalah imatinib yang merupakan tirosin kinase inhibitor. Meskipun imatinib memiliki kemampuan klinis superior, diperkirakan sekitar 20-30% pasien LGK resisten terhadap terapi imatinib,yang salah satu penyebabnya terkait ekspresi P-gp berlebih, sehingga memompakan imatinib intraseluler ke domain ekstraseluler. P-gp disandi oleh gen ABCB1 yang bersifat sangat polimorfik, tiga single nucleotide polymorphism (SNP) telah diteliti pada pasien LGK, yaitu C1236T, C3435T dan G2677T/A. Mutasi yang paling umum terjadi untuk memprediksi respons klinis terapi imatinib pada pasien LGK Asia adalah mutasi C1236T. Penelitian ini bertujuan untuk mengetahui hubungan mutasi C1236T gen ABCB1 dengan pencapaian MMR pada pasien LGK fase kronik yang mendapat imatinib.Metode: Penelitian ini merupakan penelitian potong lintang (cross-sectional) menggunakan 120 sampel darah pada pasien LGK fase kronik yang mendapat imatinib mesilat selama ≥ 12 bulan yang memenuhi kriteria seleksi. Dilakukan amplifikasi dengan metode PCR dilanjutkan dengan sekuensing metode Sanger untuk penentuan mutasi C1236T gen ABCB1.Hasil: Dari 120 sampel darah yang memenuhi kriteria seleksi dan dianalisis. Terdapat 28,3% pasien LGK fase kronik yang mencapai MMR. Mutasi C1236T adalah 72 pasien (60%). Tidak terdapat hubungan mutasi dengan pencapaian MMR (risiko prevalensi 0,717 [0,275-1,461], p = 0,282).Kesimpulan: Tidak terdapat hubungan antara mutasi C1236T gen ABCB1 pada pasien LGK fase kronik yang mendapat imatinib 12 bulan dengan pencapaian MMR.

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Chronic myeloid leukemia (CML) is one of the hematological malignancy disease which prevalence may continue to increase in the future. The treatment option of CML recently is imatinib, the tyrosine kinase inhibitor. Despite its superior clinical performance, imatinib drug resistance is developed in 20-30% patient, one of the causes is related to over expression of P-gp that transfer intracelluler imatinib to the extracelluler domain. P-gp is encoded by ABCB1 gene which is highly polymorphic. Three ABCB1 gene single nucleotide polymorphism (SNP), has been studied in CML patient; C1236T, C3435T, and G2677T/A. The most common mutation that can predict the clinical respond of imatinib therapy in Asian CML patient is C1236T mutation. This study purpose is to find the association between C1236T mutation in ABCB1 gene to the achievement of MMR in chronic phase.

Methods: This is a cross-sectional study using 120 blood samples of chronic phase CML patient who received imatinib mesylate for up to 12 months and met the selection criteria. The amplification process with PCR methods was performed, followed by Sanger methods of sequencing to determine the C1236T gene ABCB1 mutation.

Results: A total of 120 blood samples that met the selection criteria was obtained and analyzed. About 28,3% of chronic phase CML patient achieved the MMR. C1236T mutation was found in 72 patients (60%). There was no association between mutation and MMR achievement (prevalence risk 0,717 [0,275-1,461] p = 0,282]).

Conclusion: There was no association between C1236T gene ABCB1 mutation of chronic phase CML patient who received imatinib 12 months with the MMR achievement."