Pengaruh single nucleotide polymorphism gen AGT rs699 terhadap efektivitas terapi kaptropil pada pasien hipertensi di indonesia

SEPTIAYU DWI HARTIENAH, Prof. Dr. apt. Zullies Ikawati; Dr. apt. Muthi‘ Ikawati, M.Sc.

2023 | Tesis | S2 Mag.Farmasi Klinik

Hipertensi masih menjadi masalah utama dalam dunia kesehatan. Prevalensi hipertensi di Indonesia terus meningkat hingga saat ini mencapai 34,11%. Penggunaan antihipertensi golongan Angiotensin Converting Enzyme inhibitor (ACEi) seperti kaptopril sebagai salah satu lini pertama antihipertensi memiliki respon klinis yang bervariasi. Berbagai penelitian telah mengaitkan alel T dari Single Nucleotide Polymorphism (SNP) gen AGT rs699 dengan peningkatan kadar angiotensinogen dalam plasma sehingga mempengaruhi respon ACEi. Penelitian ini bertujuan untuk mengkaji distribusi frekuensi SNP AGT rs699 dan pengaruhnya terhadap efektivitas terapi kaptopril pada pasien hipertensi di Indonesia.

Total 142 pasien hipertensi pengguna kaptopril di Yogyakarta dan Bali dilibatkan dalam penelitian case-control ini. DNA diisolasi dari sampel darah 69 pasien yang mencapai target tekanan darah (kelompok kontrol) dan 73 pasien yang tidak mencapai target tekanan darah (kelompok kasus). SNP AGT rs699 diidentifikasi menggunakan metode Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) dan visualisasi menggunakan elektroforesis gel agarose. Hardy-Weinberg Equilibrium (HWE) digunakan untuk menghitung proporsi frekuensi alel. Analisis dengan uji Chi square untuk membandingkan frekuensi genotip antara kedua kelompok. Hubungan antara SNP AGT rs699 dengan efektivitas terapi ACEi dianalisis dengan perhitungan Odds Ratio (OR) dengan Confidence Interval (CI) 95%.

Distribusi frekuensi genotip seluruhan pasien hipertensi yaitu MM (10,56%); MT (32,39%); TT (57,04%). Frekuensi genotip berbeda signifikan (p<0 xss=removed xss=removed xss=removed xss=removed>

Hypertension is still a major problem in the world of health. The prevalence of hypertension in Indonesia continues to increase and currently reaches 34.11%. The use of Angiotensin Converting Enzyme inhibitor (ACEi) antihypertensives such as captopril as a first-line antihypertensive has varied clinical responses. Various studies have suggested the T allele of the Single Nucleotide Polymorphism (SNP) AGT rs699 gene with increased levels of angiotensinogen in plasma thereby affecting the ACEi response. This study aims to examine the frequency distribution of SNP AGT rs699 and its influence on the effectiveness of captopril therapy in hypertensive patients in Indonesia.

A total of 142 hypertensive patients using captopril in Yogyakarta and Bali were involved in this case-control study. DNA isolation was carried out on blood samples from 69 patients who reached the blood pressure target (control group) and 73 patients who did not reach the blood pressure target (case group). SNP AGT rs699 was identified using the Polymerase Chain Reaction - Restriction Fragment length Polymorphism (PCR-RFLP) method and visualization using agarose gel electrophoresis. Hardy-Weinberg Equilibrium (HWE) was used to calculate the proportion of allele frequencies. Analysis using Chi square test to compare genotype frequencies between the two groups. The relationship between SNP AGT rs699 and the effectiveness of ACEi therapy was explained by calculating the Odds Ratio (OR) with a 95% Confidence Interval (CI). Genotype frequency distribution of hypertensive patients is MM (10.56%); MT (32.39%); TT (57.04%). The genotype frequencies were significantly different (p<0 xss=removed xss=removed xss=removed xss=removed>

Kata Kunci : Hipertensi, Single Nucleotide Polymorphism, gen angiotensinogen (AGT), rs699, kaptopril.