POLIMORFISME -344T/C GEN ALDOSTERONE SYNTHASE DAN KADAR ALDOSTERON PLASMA PADA INDIVIDU DENGAN RIWAYAT KELUARGA HIPERTENSI

IKA SETYAWATI, Dr. Dra. Sunarti, M.Kes.

2015 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Hipertensi merupakan penyakit multifaktorial yang melibatkan faktor genetik dan lingkungan. Faktor genetik berperan penting dalam penentuan penyakit hipertensi dalam suatu keluarga. Riwayat keluarga diketahui sebagai salah satu faktor risiko terjadinya hipertensi. Gen Aldosterone synthase merupakan gen penyandi aldosteron sintase. Polimorfisme -344T/C gen aldosterone synthase telah dilaporkan di berbagai populasi dan berkaitan erat dengan kejadian hipertensi. Individu pembawa alel C dengan riwayat keluarga hipertensi berisiko menderita hipertensi. Tujuan Penelitian: Penelitian ini bertujuan untuk mengetahui polimorfisme -344T/C gen aldosterone synthase dan kadar aldosteron plasma pada individu dengan riwayat keluarga hipertensi dan tanpa hipertensi. Metode: Penelitian ini menggunakan rancangan kasus kontrol. Subjek yang diteliti yaitu individu sehat dengan riwayat keluarga hipertensi sebagai subjek kasus (n=42) dan subjek kontrol yaitu individu tanpa riwayat keluarga hipertensi (n=41). Kadar aldosteron plasma dianalisis dengan enzyme-linked immunoabsobent assay (ELISA) dan polimorfisme dengan polymerase chain reaction-restriction fragment lenght polymorfisme (PCR-RFLP). Data dianalisis dengan Independent Sampel T-test, Mann Whitney U-test, Chi-Square test dan Kruskal-Wallis test dengan tingkat signifikansi p < 0,05. Hasil: Frekuensi genotip TC+CC pada kasus lebih tinggi daripada kontrol (45,2%dan24,4%) (p=0,046). Risiko untuk mendapatkan genotip TC+CC 2,56 kali lebih tinggi pada kasus daripada kontrol (p = 0,046, OR 2,56, IK 95% 1,00-6,53). Frekuensi alel C pada kasus lebih tinggi daripada kontrol (26,2% dan 13,4%) (p=0,039). Risiko untuk mendapatkan alel C 2,29 kali lebih tinggi pada kasus daripada kontrol (p=0,039, OR 2,29, IK 95% 1,03-5,10). Kadar aldosteron plasma pada kasus (46,70 ± 31,52) lebih tinggi daripada kontrol (42,74 ±27,06) (p=0,616) dan kadar aldosteron plasma individu dengan individu dengan genotip CC lebih tinggi (52,10 ± 26,31) daripada genotip TC (46,02 ± 33,84) dan TT (43,61 ± 27,63) pada subjek penelitian (p = 0,774). Kesimpulan: Individu dengan riwayat keluarga hipertensi mempunyai risiko lebih tinggi untuk mendapatkan genotip TC+CC dan alel C dibandingkan individu tanpa riwayat keluarga hipertensi. Kadar aldosteron plasma pada subjek pembawa genotip TT, TC, dan CC tidak signifikan. Kata kunci: Hipertensi, Polimorfisme -344T/C gen aldosterone synthase, aldosteron

Background: Hypertension is a multi-factorial disease involving genetic and environmental factors. Genetic factors play an important role in the determination of hypertensive disease in a family. Family history is known as one of the risk factors of hypertension. Aldosterone synthase gene is a gene encoding aldosterone synthase. The -344T/C polymorphism of aldosterone synthase gene has been reported in various populations and closely related to the incidence of hypertension. Individuals with TC+CC genotype and C allele with family history of hypertension risks of developing hypertension. Objective: This study aimed to determine the -344T/C polymorphism of aldosterone synthase gene and plasma aldosterone levels in individuals with a family history of hypertension and without hypertension. Methods: This study used a case-control design. Subjects studied were healthy individuals with a family history of hypertension as case subjects (n = 42) and control subjects are individuals without a family history of hypertension (n = 41). Plasma aldosterone levels was analyzed by enzyme-linked immunoabsobent assay (ELISA) and polymorphism by polymerase chain reaction-restriction fragment lenght polymorphism (PCR-RFLP). The data were analyzed by Independent Sample T-test, Mann Whitney U-test, Chi-Square test and the Kruskal-Wallis test with a significance level of p < 0.05. Results: The frequency of TC + CC genotype in the case is higher than controls (45.2% and 24.4%) (p = 0.046). Risk to get a TC + CC genotype is 2.56 times higher in cases than controls (p = 0.046, OR 2.56, 95% CI 1.00 to 6.53). The frequency of allele C in the case is higher than controls (26.2% and 13.4%) (p = 0.039). The risk to get the C allele of 2.29 times higher in cases than controls (p = 0.039, OR 2.29, 95% CI 1.03 to 5.10). Plasma aldosterone levels at 42.35 cases (3.7 to 152.1) is higher than the controls 34.9 (5.9 to 111.70) (p = 0.616) and plasma aldosterone levels of individuals with CC genotype individuals with higher (48.29 (28,9-83)) than the TC genotype (40.8 (5,4-152,1)) and TT (35.2 (3,7-119,2)) on the subject of the study (p = 0.774). Conclusions: Individuals with a family history of hypertension have a higher risk to get the TC+CC genotype and C allele compared to individuals without a family history of hypertension. Plasma aldosterone levels in subjects carriers of genotype TT, TC, and CC is not significant. Keywords: Hypertension, the -344T/C polymorphism of aldosterone synthase gene, aldosterone

Kata Kunci : Hipertensi, Polimorfisme -344T/C gen aldosterone synthase, aldosteron;