Implikasi Polimorfisme Gen CYP2A6 terhadap Penyakit Kardiovaskular
Abstract
Gen CYP2A6 merupakan penyandi enzim CYP2A6. Gen CYP2A6 diketahui memiliki tingkat polimorfisme yang tinggi sehingga menyebabkan terdapatnya variasi bentuk alel baik dalam bentuk aktif maupun alel inaktif. Adanya variasi bentuk alel ini selanjutnya dapat berakibat pada penurunan, peningkatan atau penghilangan aktivitas enzim CYP2A6 yang disandi oleh gen ini. Salah satu substrat spesifik enzim CYP2A6 adalah nikotin, suatu senyawa aktif terdapat dalam rokok. Nikotin diketahui merupakan salah satu faktor risiko penyakit kardiovasakuler, sehingga kehadiran alel inaktif gen CYP2A6 akan menyebabkan penurunan aktivitas enzim CYP2A6 dalam metabolisme nikotin dan lebih lanjut akan meningkatkan risiko penyakit kardiovaskuler. Tujuan dari artikel review ini yaitu untuk mengevaluasi implikasi polimorfisme gen CYP2A6 terhadap penyakit kardiovaskular. Database yang digunakan pada artikel review ini berasal dari PubMed dan Google Scholar yang kemudian dilakukan seleksi dengan menggunakan kriteria inklusi dan eksklusi. Hasil yang diperoleh yaitu terdapat pengaruh polimorfisme gen CYP2A6 terhadap kandungan nikotin dalam darah terutama pada individu dengan gen CYP2A6 yang memiliki aktivitas metabolisme yang lambat atau buruk yang mengakibatkan kadar nikotin dalam darah yang tinggi, yang kemudian mengakibatkan peningkatan pengaktifan sistem saraf simpatis, lipolisis, dan resistensi insulin yang menyebabkan peningkatan kejadian anterosklerosis. Disimpulkan bahwa polimorfisme gen CYP2A6 akan meningkatkan penyakit kardiovaskuler terutama pada perokok, baik aktif maupun pasif.
Kata kunci: Atherosklerosis, CYP2A6, penyakit kardiovasuler, polimorfisme
The Effects of CYP2A6 Gene Polymorphism on Cardiovascular Diseases
Abstract
The CYP2A6 gene encodes its enzymes and is highly polymorphic, leading to variations in allele forms, both in the active and inactive states. These changes result in a decrease, increase or deletion of enzyme activities. One of the specific substrates is nicotine, an active compound in cigarettes. Nicotine is a major risk factor for cardiovascular diseases, and the inactive alleles tends to decrease its metabolism and expands the threat to infections. Therefore, this study aims to evaluate the effects of CYP2A6gene polymorphism on cardiovascular diseases. Relevant literatures were obtained using PubMed and Google Scholar, while the eventual selection followed the inclusion and exclusion criteria. Based on this review, the CYP2A6 gene polymorphism, both in increased, decreased or deleted alleles, was known to significantly influence nicotine metabolism and its blood levels. Species categorized as slow or poor metabolizers, tend to decrease the nicotine metabolism, but result in greater nicotine blood levels. This outcome subsequently accelerated the activation of the sympathetic nervous system, lipolysis, and insulin resistance, to trigger atherosclerosis. In summary, CYP2A6 gene polymorphism is known to increase cardiovascular diseases, particularly among active or passive smokers.
Keywords: Atherosclerosis, cardiovascular disease, CYP2A6, polymorphism
Keywords
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DOI: https://doi.org/10.15416/ijcp.2021.10.3.217
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