IJPTher, Volume 4, Number 3, 2023; *corresponding author: zullies_ikawati@ugm.ac.id ISSN 2745-455X (Online) Indonesian Journal of Pharmacology and Therapy Keywords: hypertension; ACE I/D gene polymorphism; ACE inhibitor; angiotensin-converting enzyme; response Submitted: 25-05-2023 Accepted : 10-06-2023 The role of angiotensin I - converting enzyme (ACE) insertion/deletion gene polymorphism in hypertension and ACE inhibitor therapy: a narrative review Dewa Ayu Sri Handani 1 , Zullies Ikawati 1,2 *, Adam Hermawan 1,3 1 Magister of Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia, 2 Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia, 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia https://doi.org/10.22146/ijpther.8281 ABSTRACT Primary hypertension is the most prevalent type of hypertension, which is primarily attributed to genetic factors. The angiotensin-converting enzyme (ACE) gene has emerged as a prominent candidate among the genetic factors influencing blood pressure regulation. The ACE gene encodes the ACE, which plays a crucial role in the renin-angiotensin system. The ACE gene insertion/ deletion (I/D) polymorphism is a variation of the ACE gene that affects blood pressure regulation. Individuals with II, ID, and DD genotypes may exhibit distinct ACE plasma concentrations, potentially contributing to variations in blood pressure levels and response to ACE inhibitor therapy. This article aimed to provide a comprehensive overview of the relationship between the ACE I/D gene with hypertension and angiotensin-converting enzym inhibitor (ACEI) effectiveness. This article presents a narrative review encompassing relevant studies published between 2013 and 2023. A systematic search was conducted using reputable databases such as PubMed, Science Direct, and Scopus. Inclusion criteria were applied, resulting in the selection of 25 articles that met the predefined criteria. The analysis included 25 studies, comprising 5 articles that investigated the impact of ACEI therapy and 20 articles that examined the ACE I/D gene polymorphism in hypertensive populations without ACEI therapy. It can be concluded that compared to the I allele, the D allele of the ACE I/D gene is associated with a higher level of essential hypertension and a reduced ACEI response. ABSTRAK Hipertensi primer adalah jenis hipertensi yang paling umum, terutama disebabkan oleh faktor genetik. Gen angiotensin-converting enzyme (ACE) merupakan kandidat gen utama di antara faktor genetik yang mempengaruhi pengaturan tekanan darah. Gene ACE mengkode ACE, yang memiliki peran penting dalam sistem renin-angiotensin. Polimorfisme insersi/delesi (I/D) gen ACE adalah variasi gen ACE yang memiliki dampak pada regulasi tekanan darah. Individu dengan genotipe II, ID, dan DD dapat menunjukkan konsentrasi plasma ACE yang berbeda. Polimerfisme ini berpotensi berkontribusi terhadap variasi tingkat tekanan darah dan respons terhadap terapi penghambat angiotensin- convertinn enzyme (ACEI). Telaah artikel ini bertujuan untuk memberikan gambaran yang komprehensif tentang hubungan antara gen ACE I/D dengan hipertensi dan efektivitas ACEI. Artikel ini menyajikan ulasan naratif yang mencakup penelitian relevan antara tahun 2013 dan 2023. Pencarian sistematis dilakukan menggunakan database terkemuka seperti PubMed, Science Direct, dan Scopus. Kriteria inklusi diterapkan, menghasilkan pemilihan 25 artikel yang memenuhi kriteria yang telah ditentukan. Analisis tersebut mencakup 25 penelitian, yang terdiri dari 5 artikel tentang efek terapi ACEI dan 20 artikel tentang polimorfisme gen ACE I/D pada populasi hipertensi tanpa terapi ACEI. Dapat disimpulkan bahwa dibandingkan dengan alel I, alel D dari gen ACE I/D terkait dengan tingkat hipertensi esensial yang lebih tinggi dan respons ACEI yang berkurang.