Kajian Pengaruh Polimorfisme CYP4F2 rs2108622 terhadap Pemberian Dosis Warfarin
DOI:
https://doi.org/10.29313/jrf.v2i2.1171Keywords:
Warfarin, CYP4F2, rs2108622Abstract
Abstract. Warfarin is an oral anticoagulant drug indicated for the treatment of thromboembolism. Warfarin has a narrow therapeutic index, so care must be taken in determining the dose of warfarin for the patient. The effect of anticoagulant therapy produced by warfarin in individuals may vary due to the influence of the CYP4F2 polymorphism rs2108622 which causes changes in the C > T allele. and the genomic database from Ensembl. The results showed that individuals with the CYP4F2 polymorphism rs2108622 required a higher dose of warfarin than the normal allele. In addition, the frequency of the CYP4F2 rs2108622 polymorphism in Asian ethnicities is low. From the results obtained, it can be concluded that the CYP4F2 polymorphism strongly influences the dose of warfarin and the frequency of the polymorphism in Asia is low.
Abstrak. Warfarin merupakan obat antikoagulan oral yang diindikasikan untuk terapi tromboembolisme. Warfarin memiliki indeks terapeutik yang sempit sehingga dibutuhkan kecermatan dalam menentukan dosis warfarin untuk pasien. Efek terapi antikoagulan yang dihasilkan oleh warfarin pada individu dapat bervariasi yang disebabkan adanya pengaruh dari polimorfisme CYP4F2 rs2108622 yang menyebabkan perubahan alel C > T. Penelitian ini bertujuan untuk mengkaji pengaruh polimorfisme CYP4F2 rs2108622 terhadap pemberian dosis warfarin dengan menggunakan data dari artikel ilmiah internasional dan nasional bereputasi serta database genomik dari Ensembl. Hasil penelitian menunjukkan bahwa individu dengan polimorfisme CYP4F2 rs2108622 membutuhkan dosis warfarin yang lebih tinggi dibandingkan dengan alel normal. Selain itu, frekuensi polimorfisme CYP4F2 rs2108622 pada etnis Asia rendah. Dari hasil yang diperoleh, dapat disimpulkan bahwa polimorfisme CYP4F2 sangat berpengaruh terhadap pemberian dosis warfarin dan frekuensi polimorfisme tersebut di Asia rendah.
References
L. H. Cavallari and K. M. Momary, Pharmacogenetics in cardiovascular diseases. 2018.
S. U. Rahmayanti and A. Muhtadi, “Review Jurnal: Interaksi Warfarin Dan Herbal Untuk Meminimalkan Kejadian Adverse Drug Reaction (Adr),” J. Farmaka, vol. 16, no. 2, pp. 233–245, 2018.
R. K. Bains, “African variation at Cytochrome P450 genes,” Evol. Med. Public Heal., vol. 2013, no. 1, pp. 118–134, 2013, doi: 10.1093/emph/eot010.
H. Raunio, M. Kuusisto, R. O. Juvonen, and O. T. Pentikäinen, “Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes,” Front. Physiol., vol. 6, no. JUNE, pp. 1–14, 2015, doi: 10.3389/fphar.2015.00123.
M. W. Jann, S. R. Penzak, and L. J. Cohen, Applied clinical pharmacokinetics and pharmacodynamics of psychopharmacological agents. Fort Worth: Springer International Publishing Switzerland, 2016.
D. W. Nebert and D. W. Russell, “Clinical importance of the cytochromes P450,” Lancet, vol. 360, no. 9340, pp. 1155–1162, 2002, doi: 10.1016/S0140-6736(02)11203-7.
D. P. Sari and F. Ferdiansyah, “Variasi Frekuensi Alel Terkait Polimorfisme CYP4F2 dan CYP2C9 (* 2 ,* 3 ) pada Berbagai Etnis di Dunia : Review,” Indones. J. Appl. Sci., vol. 7, pp. 73–76, 2017, doi: https://doi.org/10.24198/.v7i3.8599.g8140.
T. Zhang, K. Yu, and X. Li, “Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) rs1558139, rs2108622 polymorphisms and susceptibility to several cardiovascular and cerebrovascular diseases,” BMC Cardiovasc. Disord., vol. 18, no. 1, pp. 1–10, 2018, doi: 10.1186/s12872-018-0763-y.
M. D. Caldwell et al., “CYP4F2 genetic variant alters required warfarin dose,” Blood First Ed. Pap. J., vol. 111, no. 8, pp. 4106–4113, 2008, doi: 10.1182/blood-2007-11-122010.The.
M. G. McDonald, M. J. Rieder, M. Nakano, C. K. Hsia, and A. E. Rettie, “CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant,” Mol. Pharmacol., vol. 75, no. 6, pp. 1337–1346, 2009, doi: 10.1124/mol.109.054833.
M. L. Alvarellos, K. Sangkuhl, R. Daneshjou, M. Whirl-carrillo, R. B. Altman, and T. E. Klein, “PharmGKB summary : very important pharmacogene information for CYP4F2,” Liipincott Williams & Wilkins, vol. 25, pp. 41–47, 2015, doi: 10.1097/FPC.0000000000000100.
L. N. Al-eitan, A. Y. Almasri, A. H. Alnaamneh, H. A. Aman, and N. N. Alrabadi, “Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility to cardiovascular disease in Jordan,” Int. J. Med. Sci., vol. 18, pp. 826–834, 2021, doi: 10.7150/ijms.51546.
W. Ageno, A. S. Gallus, A. Wittkowsky, M. Crowther, E. M. Hylek, and G. Palareti, “Oral anticoagulant therapy - Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines,” Chest, vol. 141, no. 2 SUPPL., pp. e44S-e88S, 2012, doi: 10.1378/chest.11-2292.
A. Di Minno et al., “Old and new oral anticoagulants: Food, herbal medicines and drug interactions,” Blood Rev., vol. 31, no. 4, pp. 193–203, 2017, doi: 10.1016/j.blre.2017.02.001.
T. Rusdiana, T. Araki, T. Nakamura, A. Subarnas, and K. Yamamoto, “Responsiveness to low-dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population,” Eur. J. Clin. Pharmacol., vol. 69, no. 3, pp. 395–405, 2013, doi: 10.1007/s00228-012-1356-9.
J. A. Johnson et al., “Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update,” Clin. Pharmacol. Ther., vol. 102, no. 3, pp. 397–404, 2017, doi: 10.1002/cpt.668.
H. J. Cen et al., “CYP4F2 rs2108622: A minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement,” Br. J. Clin. Pharmacol., vol. 70, no. 2, pp. 234–240, 2010, doi: 10.1111/j.1365-2125.2010.03698.x.
X. Sun, W. Y. Yu, W. Le Ma, L. H. Huang, and G. P. Yang, “Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis,” Biomed. Reports, vol. 4, no. 4, pp. 498–506, 2016, doi: 10.3892/br.2016.599.
J. Li, W. Yang, Z. Xie, K. Yu, Y. Chen, and K. Cui, “Impact of VKORC1, CYP4F2 and NQO1 gene variants on warfarin dose requirement in Han Chinese patients with catheter ablation for atrial fibrillation,” BMC Cardiovasc. Disord., vol. 18, no. 1, pp. 2–7, 2018, doi: 10.1186/s12872-018-0837-x.
D. S. T. Nicholl, An Introduction to Genetic Engineering, Third Edit. New York: Cambridge University Press, 2008.
