POLIMORFISME GEN ANGIOTENSIN I CONVERTING ENZYME (ACE) INSERSI/DELESI (I/D) DAN HEIPERTENSI PADA PENDUDUK MLATI SLEMAN (Tinjauan Pustaka dan Laporan Penelitian)

SUTARSO KAMAJAYA, Prof. Dr. dr. Moch. Sja'bani, M.Med.Sc., SpPD-KGH

2011 | Tesis | S2 Ked.Klinik/MS-PPDS

Latar Belakang: Hipertensi merupakan hasil interaksi komplek dari faktor genetik dan lingkungan. Kejadian perubahan genetik sangat jarang, bila perubahan genetik terjadi lebih dari 1% populasi disebut polimorfisme. Polimorfisme gen-gen yang mengkode komponen Reninangiotensin- aldosteron system (RAAS) berperan timbulnya hipertensi esensial. Polimorfisme yang paling populer adalah insersi/delesi (I/D) gen-ACE. Dalam beberapa penelitian didapatkan genotip DD dan alel-D berhubungan dengan hipertensi esensial. Terdapat perbedaan yang luas polimorfisme gen-ACE pada etnis yang berbeda. Di Indonesia belum pernah dilaporkan polimorfisme gen-ACE pada hipertensi yang berbasis komunitas. Tujuan Penelitian: Mengetahui seberapa besar polimorfisme gen-ACE I/D pada pasien hipertensi pada populasi Jawa. Metode: Penelitian secara case contol dengan matching umur dan jenis kelamin pada komunitas di Mlati-Sleman-Yogyakarta. Waktu penelitian Agustus 2008 sampai Juli 2009. Dari 12073 subyek berumur lebih 17 tahun yang diteliti, diambil sampel yang berumur 30-59 tahun berjumlah 7695 orang dan dikelompokkan dalam normotensi, pre-hipertensi dan hipertensi. Dilakukan pengacakan terstratifikasi, diambil sampel hipertensi 51 orang dan normotensi 51 orang. Pemeriksaan molekuler dengan metode polymerase chain reaction (PCR) di laboratorium Biokimia FK-UGM. Hasil: Frekuensi genotip dan alel pada populasi hipertensi dan normotensi adalah II 23(45,0%) vs 37(72,5%), ID 25(49,0%) vs 13(25,5 %) dan DD 3(6,0 %) vs 1(2,0 %) p=0,043. Frekuensi alel pada hipertensi adalah alel-I 35(68,5%) vs 43(84,5%), alel-D 16(31,5%) vs 8(15,5%) p=0.038. Analisis regresi logistik menunjukkan alel-D merupakan faktor risiko terjadinya hipertensi. Kesimpulan: Frekuensi genotip ID dan DD serta alel-D dari polimorfisme gen-ACE lebih tinggi pada hipertensi daripada normotensi. Alel D merupakan faktor risiko terjadinya hipertensi.

Background: Hypertension is considered as a multifactorial trait resulting from a combination of environmental and genetic factors. Genetic mutation is rare, when genetic mutation more than 1% population called as polymorphism. There are many genes polymorphism associated with hypertension. Polymorphism of the genes coded in the component of Renin-angiotensinaldosteron system (RAAS) are potential influence essential hypertension. The popular polymorphism was a insertion/deletion (I/D) in ACE gene. Recent studies showed that DD genotype and D allele have been associated with higher prevalence of hypertension. There is no data reported so far about the possible effect of I/D polymorphism of the ACE gene and hypertension in Javanese population based on community. There is a wide variation in ACE gene polymorphism among the ethnics. Objective: To investigate ACE gene polymorphism in hypertensive subjects in Javanese population. Methode: A case control study by matching of sex and age, was conducted in August 2008-July 2009, based on community at district of Sleman-Yogyakarta. The covered subjects were 12073 over 17 years, after selected by aged of 30-59 years old, we get 7695 people and grouped in normotension, pre-hypertension and hypertension. Stratified randomize was done to select 51 for hypertension and 51 normotension involving this study. Genotypes based on the polymorphisms (II/ID/DD) using a polymerase chain reaction (PCR) methode, at Biochemistry Laboratory Faculty of Medicine Gadjah Mada University Yogyakarta. Results: The genotype frequencies in hypertensive group versus normal were II 23(45.0%) vs 37(72.5%), ID 25(49.0%) vs 13(25.5%) and DD 3(6.0%) vs 1(2.0%) p=0.043. The allele frequencies were I allele 35(68.5%) vs 43(84.5%), D allele 16(31.5%) vs 8(15.5%), p=0.038. Logistic regression analysis showed that D allele as a risk factor for hypertension. Conclusion: Frequencies of ID and DD genotypes and D allele ACE gene in hypertensive subject were higher than normotensive subjects. The D allele of the ACE gene was a predisposing factor in hypertension.

Kata Kunci : polimorfisme gen-ACE, sistem-RAA, hipertensi