Pharmacogenomics and Precision Pharmacotherapy in Heart Failure: A Narrative Review
DOI:
https://doi.org/10.56951/51m6s534Kata Kunci:
gagal jantung, farmakogenomik, kedokteran presisi, polimorfisme nukleotida tunggal, farmakoterapi kardiovaskularAbstrak
Gagal jantung merupakan kondisi yang mengancam jiwa, dengan prevalensi mencapai sekitar 1% dari populasi global dan terus menunjukkan tren peningkatan. Faktor genetik, termasuk varian patogenik pada gen sarkomer, sitoskeletal, dan kanal ion, berperan dalam progresivitas penyakit ini, yang umumnya mengikuti pola pewarisan Mendel. Namun demikian, sebagian besar variabilitas antarindividu dalam perjalanan penyakit maupun respons terapi justru berasal dari pola poligenik non-Mendel, terutama polimorfisme nukleotida tunggal atau single nucleotide polymorphism (SNP). SNP dapat memengaruhi ekspresi gen, fungsi protein, dan jalur persinyalan hilir secara moderat, sehingga pada akhirnya berdampak pada farmakokinetika dan farmakodinamika obat-obatan kardiovaskular. Varian pada gen seperti CYP2D6, ACE, AGT, CYP11B2, ADRB1/2, SLC5A2, dan UGT2B4 telah dikaitkan dengan perbedaan respons terhadap β-blocker, SGLT2-inhibitors dan penghambat angiotensin converting enzyme (ACE). Penerapan pendekatan genomik dalam praktik klinis masih terbatas, antara lain karena ukuran studi yang kecil, variabilitas antarindividu yang tinggi, serta belum adanya biomarker yang terstandardisasi. Meskipun demikian, integrasi data genetik, epigenetik, dan fenotipik menawarkan strategi yang menjanjikan untuk mengarahkan farmakoterapi gagal jantung ke arah yang lebih efektif dan bersifat individual.
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