POLIMORFISME GEN ANGIOTENSIN II TYPE 1 RECEPTOR (AGTR 1) DAN GEN ANGIOTENSIN CONVERTING ENZYME (ACE) PADA INDIVIDU DENGAN RIWAYAT KELUARGA HIPERTENSI

MUTMAINNAH ABBAS, Dr. Sunarti, M.Kes.

2015 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang. Riskesdas tahun 2013 melaporkan bahwa penderita hipertensi di Indonesia mencapai 25,8% dan di DI Yogyakarta sebesar 25,7%. Gen AGTR1 dan gen ACE merupakan gen kandidat pada patogenesis hipertensi. Polimorfisme gen AGTR1 dan gen ACE dapat menyebabkan peningkatan tekanan darah pada orang dewasa. Dengan mengetahui adanya polimorfisme gen-gen tersebut pada individu dengan riwayat keluarga hipertensi dapat menjadi upaya pencegahan meningkatnya prevalensi hipertensi. Tujuan. Mengetahui frekuensi polimorfisme gen AGTR1 dan gen ACE sebagai faktor risiko terjadinya hipertensi pada individu dengan riwayat keluarga hipertensi. Metode. Jenis penelitian ini adalah case-control study yang melibatkan 46 subjek dengan riwayat keluarga hipertensi dan 46 subjek tanpa riwayat keluarga hipertensi (kontrol). Subjek penelitian usia dewasa ≥ 18-35 tahun yang memiliki tekanan darah normal. Pemeriksaan genotip gen AGTR1 menggunakan metode Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) dan genotip gen ACE menggunakan metode Polymerase Chain Reaction (PCR). Hasil. Frekuensi genotip gen AGTR1 pada kelompok kasus adalah genotip AA sebesar 89,1% dan AC sebesar 10,9%, pada kontrol genotip AA sebesar 87% dan genotip AC sebesar 13% (p = 0,748). Odds Ratio (OR) genotip sebesar 0,813. Frekuensi alel A pada kelompok kasus sebesar 94,6% dan alel C sebesar 5,4%, pada kelompok kontrol alel A sebesar 93,5% dan alel C sebesar 6,5% (p = 0,756). Odds Ratio (OR) alel sebesar 1,214. Frekuensi genotip gen ACE pada kelompok kasus adalah genotip II sebesar 54,3%, genotip DD sebesar 15,2%, pada kelompok kontrol genotip II sebesar 56,5%, genotip DD sebesar 6,5% (p = 0,834). Odds Ratio (OR) genotip sebesar 1,092. Frekuensi alel I pada kelompok kasus sebesar 69,6% dan alel D sebesar 30,4%, pada kelompok kontrol alel I sebesar 75% dan alel D sebesar 25% (p = 0,410). Odds Ratio (OR) alel sebesar 1,313. Kesimpulan. Hasil ini menunjukkan bahwa individu dengan riwayat keluarga hipertensi kurang berisiko membawa alel varian C polimorfisme gen AGTR1 dan alel varian D polimorfisme gen ACE pada etnis Jawa. Kata Kunci: Hipertensi, sistem renin angiotensin aldosteron, polimorfisme gen AGTR1, polimorfisme gen ACE

Background- Riskesdas 2013 reported that patients with hypertension in Indonesia reached 25.8% and particularly in Yogyakarta by 25.7%. ACE gene polymorphism may increase plasma ACE levels which can inactivate bradykinin. Angiotensin II is formed by the presence of ACE acts as a vasoconstrictor that will bind to receptors of the angiotensin II type 1 which is a transmembrane receptor that plays a role in signal transduction and can affect blood pressure variation. AGTR1 gene polymorphisms may cause an increase in blood pressure for adults. By knowing their AGTR1 gene polymorphism and ACE gene polymorphism for adults with a family history of hypertension may be preventing the increasing prevalence of hypertension. Objective- Knowing the frequency of AGTR1 gene polymorphism and ACE gene polymorphism as the risk factor for hypertension in individuals with a descent history of hypertension. Method- This is a case-control study which is involving 46 subjects with hypertension history and 46 subjects without a history of hypertension (control). Research subjects of adulthood were more than or equivalent (≥) to 18-35 years who have normal blood pressure. The inspection of AGTR1 gene genotype (AA / AC / CC) is using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Likely, the inspection of the genotype of ACE gene is using PCR method. Result- Genotype frequency in the group of the family history of hypertension was 89.1% for genotypes AA and AC of 10.9%, the AA genotype controls by 87% and air conditioning by 13% (p = 0.748). Odds Ratio (OR) of genotype was 0,813. The frequency of allele A in the group of the family history of hypertension is 94.6% and allele C of 5.4%, in the control group of allele A was 93.5% and allele C of 6.5% (p = 0.756). Odds Ratio (OR) of allele is 1,214. These results demonstrated that in subjects with a family history of hypertension are not at risk carrying the variant C allele in the population of Java. Genotype frequency in the group of family history of hypertension sequentially was 54.3% genotype II, ID 30.4%, and 15.2% DD, the control genotype II amounting to 56.5%, 37% ID, and DD 6.5% (p = 0.385). Odds Ratio (OR) of genotype was 1.092. the frequency of allele I in the group of family history of hypertension was 69.6% and 30.4% for allele D, in the control group by 75% I alleles and allele D by 75% (p = 0.410). Odds Ratio (OR) of allele is 1.313. These results described that in the subjects with a family history of hypertension are not at risk carrying the variant allele D in the population of Java. Conclusion- The frequency of AA genotype and allele A gene polymorphism of AGTR1 was higher in a group of the family history with hypertension. The frequency of the DD genotype and allele D of ACE gene polymorphism was higher in a group of the family history of hypertension. Nevertheless, it is not a risk factor for hypertension in individuals with a family history of hypertension in Java Keywords: Hypertension, Renin-Angiotensin-Aldosterone system, AGTR1 gene polymorphism, ACE gene polymorphism

Kata Kunci : Hipertensi, sistem renin angiotensin aldosteron, polimorfisme gen AGTR1, polimorfisme gen ACE; Hypertension, Renin-Angiotensin-Aldosterone system, AGTR1 gene polymorphism, ACE gene polymorphism