Wulandari, Atik Sri (2019) Peran Polimorfisme Gen Agtr1 A1166c Pada Sistem Renin Angiotensin Aldosteron Dikaitkan Faktor Risiko Hipertensi Sebagai Faktor Predisposisi Hipertensi Esensial. Doctor thesis, Universitas Brawijaya.
Abstract
Hipertensi (HT) menjadi masalah besar di dunia karena merupakan factor risiko utama pada penyakit jantung, struk dan ginjal, serta menjadi penyumbang angka terbesar untuk kematian akibat penyakit kardiovaskuler. Angka kejadian hipertensi dari waktu ke waktu cenderung meningkat, seiring dengan pergeseran angka kejadian Penyakit Tidak Menular (PTM), yang mencapai 60% seluruh kesakitandan 73% kematian di dunia.Pada tahun 2016 dilaporkan bahwa prevalensi hiperteni di Provinsi Jawa Timur adalah sebesar 13,47% atau sekitar 935.736 penduduk, dengan proporsi laki-laki sebesar 13,78% (387.913 penduduk) dan perempuan sebesar 13.25% (547.823 penduduk). Patogenesis utama terjadinya HT berpangkat pada sistem Renin – Angiotensin Aldosteron (RAA). Dalam jalur ini terdapat hormon Angiotensin II sebagai efektor utama yang berperan dalam pengaturan tekanan darah. Selain komponen dalam sistem RAA, faktor-faktor lingkungan, kebiasaan hidup dan genetik juga ikut berkontribusi pada kejadian HT. Salah satu faktor genetik yang diduga ikut berperan pada kejadian hipertensi adalah adanya polimorfisme gen-gen reseptorpadajalur RAA, antara lain adalah gen AGTR1 A1166C. Tujuan dari penelitian ini adalah menmgetahui peran AGTR 1 A1166C dan factor risiko hipertensi lainnya sebagai predisposes ihipertensi esensial. Kabupaten Sidoarjo merupakan salah satu daerah yang memiliki angka kejadian HT cukup tinggi, merupakan 10 penyakit terbanyak dan semakin meningkat. Hingga sekarang belum ada studi tentang tingginya angka HT di wilayah Sidoarjo, khususnya peran faktor genetik dan faktor risiko lain. Penelitian ini dilakukan dengan tujuan untuk menganalisis peran faktor risiko hipertensi khususnya adany polimorfisme gen AGTR1 A1166C dikaitkan dengan faktor risiko yang lain , seperti faktor lingkungan dan kebiasaan hidup. Proposal penelitan observasional ini telah mendapat pernyataan kelainan etik (Ethical Clearance) dari Komite Etik Peneltian Kesehatan (KEPK) FK UWKS No. 101109/SLE/FK/UWKS/ 2016. Penelitian dilakukan menggunakn pendekatan potong lintang (cross-sectional) dengan subyek para pengunjung Puskesman Taman Kabupaten Sidoarjo, selama bulan Septeber 2016 sampai dengan Agustus 2017. Pasien yang bersedia menjadi subyek dan telah menanda tangani informed consent pada penelitian ini, melalui wawancara dicatat data tetang umur, jenis kelamin, konsumsi garam, MSG, kebiasaan merokok. kemudian diukur tinggi dan berat badan serta tekanan darahnya, Darah diambil dari vena mediana cubiti sebanyak 15 cc, kemudian dilakukan Analisis polymorphism AGTR1 A1166C dengan Real-time PCR (ABI 7300 Real Time PCR System), Applied Biosystems, Foster City, CA with SYBR green probe (Eurogentec, Seraing, Belgium) PCR Core reagents; pemeriksaanSerum sodium (Ion Selective Electrodes (ISE), glukosa darah Glucose oxidase-Phenol Aminophenazone (GOD–PAP), dan lemak Cholesterol Oxidase-Phenol Aminophenazone (CHOD–PAP). Dari 200 orang yang pada awalnya telah menyatakan kesediaan ikut dalam penelitian, pada akhirnya tersisa 106 orang, 66 orang di antaranya mengalami hipertensi dan 40 orang normotensi. Analisis lebih lanjut menunjukkan bahwa ada hubungan antara polimorfisme AGTR1 A1166C dengan kejadian hipertensi esensial (p=0.035; CI=95%) dengan OR 4.66 (CI=95%, dari 106 subyek penelitian 91 mempunyai genotip AA, 15 genotip AC ( 13 genotip AC diantaranya mengalami hipertensi dan 2 subyek genotip AC diantaranya normotensi). Polimorfisme AGTR1 A1166C berhubungan dengan kadar natrium serum (p=0.001; CI 95%). p=0.0445). Polimorfisme AGTR1 A1166C pada genotip AC tidak berhubungan dengan kadar natrium serum (p=0.001; CI 95%). p=0.0445) dan tidak berhubungan dengan usia (p=852; CI=95%), jenis kelamin (p=0.641; CI=95%), konsumsi garam (p=0.568;CI=95%), MSG (p=0.129;CI=95%), Rokok (p=0.260;CI=95%), Indeks Masa Tubuh (IMT) (p=0.751;CI=95%), obesitas viseral (p=0.481;CI=95%), gula darah (p=0, 955.;CI=95%), trigliserida (p=0.152;CI=95%), High Density Lipoprotein (HDL) (p=0,863;CI=95%), Low Density Lipoprotein (LDL) (p=0.134;CI=95%), cholesterol (p=0.294;CI=95%). Hipertensi esensial berhubungan dengan polimorfisme AGTR1 usia (p=018; CI=95%), konsumsi garam (p=0.037;CI=95%), MSG (p=0.025;CI=95%), obesitas viseral (p=0.000;CI=95%), (p= kadar natrium serum (p=0.000; CI 95%), gula darah (p=0, 009.;CI=95%), Low Density Lipoprotein (LDL) (p=0.000;CI=95%), dan tidak berhubungan dengan jenis kelamin (p=302;CI95%), rokok (p=0.292;CI=95%), IMT (p=0.427;CI=95%), trigliserida (p=0.476;CI=95%), High Density Lipoprotein (HDL) (p=0,193;CI=95%), cholesterol (p=0.677;CI=95%). Analisis regresi menunjukkan obesitas visceral (OR=6.496), natrium Serum (OR=1.905), glucose (OR=8.529) dan LDL tinggi (OR=13.514) merupakan factor predisposisi hipertensi esensial , dengan persamaan regresi Indeks Prediktif Kejadian hipertensi berdasar factor risiko = -92.215 + 1.871 (Obes positif) + 0.644( point Natrium serum) + 2.144 (glukosadiatas normal) – 3.010 (LDL rendah) + 2.604 (LDL tinggi).
English Abstract
Hypertension (HT) is a major problem in the world because it is a major risk factor for heart disease, stroke and kidney, and is the biggest contributor to cardiovascular disease deaths. The incidence of hypertension over time tends to increase, along with the shift in the incidence of Non-Communicable Diseases (PTM), which reaches 60% of all illnesses and 73% of deaths in the world. In 2016 it was reported that the prevalence of hypertension in East Java Province was 13.47 % or around 935,736 residents, with the proportion of men at 13.78% (387,913 inhabitants) and women at 13.25% (547,823 residents). The main pathogenesis of HT occurs on the Renin - Angiotensin Aldosterone (RAA) system. In this pathway there is the Angiotensin II hormone as the main effector that plays a role in regulating blood pressure. In addition to the components in the RAA system, environmental factors, life habits and genetics also contribute to the occurrence of HT. One genetic factor that is thought to play a role in the incidence of hypertension is the presence of polymorphisms of the RAA receptor genes, including the AGTR1 A1166C gene. The aim of this study was to know the role of AGTR 1 A1166C and other hypertensive risk factors as predisposing to essential hypertension. Sidoarjo Regency is one of the regions that has a high incidence of HT, which is the 10 most diseases and is increasing. Until now there has been no study of the high rates of HT in the Sidoarjo region, specifically the role of genetic factors and other risk factors. This study was conducted with the aim of analyzing the role of hypertension risk factors, especially the AGTR1 A1166C gene polymorphism associated with other risk factors, such as environmental factors and life style. This observational research proposal has received an Ethical Clearance statement from the Health Research Ethics Committee (KEPK) FK UWKS No. 101109 / SLE / FK / UWKS / 2016. The study was conducted using a cross-sectional approach with the subjects of visitors to the Puskesman Taman Sidoarjo Regency, during September 2016 to August 2017. Patients who were willing to be subjects and signed informed consent on this study, through interviews, recorded data on age, gender, salt consumption, MSG, smoking habits. then measured the height and weight and blood pressure, blood was taken from the median cubiti vein as much as 15 cc, then performed polymorphism analysis of AGTR1 A1166C with Real-time PCR (ABI 7300 Real Time PCR System, Applied Biosystems, Foster City, CA) with SYBR green probes (Eurogentec, Seraing, Belgium) PCR Core reagents; examination of serum sodium (ion selective electrodes (ISE), blood glucose (Glucose oxidase-phenol Aminophenazone (GOD-PAP), and fat (Cholesterol Oxidase-Phenol Aminophenazone (CHOD-PAP). Of the 200 people who initially expressed their willingness to participate in the study, in the end there were 106 people left, 66 of whom had hypertension and 40 normotensive people. Further analysis showed that there was a relationship between AGTR1 A1166C polymorphism and the incidence of essential hypertension (p = 0.035; CI = 95%) with OR 4.66 (CI = 95%, of 106 research subjects 91 having AA genotype, 15 AC genotypes (13 AC genotypes including hypertension and 2 AC genotypes including normotension) AGTR1 A1166C polymorphism is associated with serum sodium levels (p = 0.001; 95% CI). p = 0.0445). The AGTR1 A1166C polymorphism in the AC genotype was not related to serum sodium levels (p = 0.001; 95% CI). p = 0.0445) and not related to age (p = 852; CI = 95%), gender (p = 0.641; CI = 95%), salt consumption (p = 0.568; CI = 95%), MSG (p = 0.129; CI = 95%), Cigarettes (p = 0.260; CI = 95%), Body Mass Index (BMI) (p = 0.751; CI = 95%), visceral obesity (p = 0.481; CI = 95%), blood sugar (p = 0, 955.; CI = 95%), triglycerides (p = 0.152; CI = 95%), High Density Lipoprotein (HDL) (p = 0.863; CI = 95%), Low Density Lipoprotein (LDL ) (p = 0.134; CI = 95%), cholesterol (p = 0.294; CI = 95%). Essential hypertension was associated with age AGTR1 polymorphism (p = 018; CI = 95%), salt consumption (p = 0.037; CI = 95%), MSG (p = 0.025; CI = 95%), visceral obesity (p = 0.000; CI = 95%), (p = serum sodium level (p = 0,000; CI 95%), blood sugar (p = 0, 009.; CI = 95%), Low Density Lipoprotein (LDL) (p = 0,000; CI = 95%), and not related to gender (p = 302; CI95%), cigarettes (p = 0.292; CI = 95%), BMI (p = 0.427; CI = 95%), triglycerides (p = 0.476; CI = 95%), High Density Lipoprotein (HDL) (p = 0.193; CI = 95%), cholesterol (p = 0.677; CI = 95%). Regression analysis showed visceral obesity (OR = 6.496), sodium Serum (OR = 1905), glucose (OR = 8,529) and high LDL (OR = 13,514) is a predisposing factor for essential hypertension, with the regression equation Predictive Index of Hypertension based on risk factors = -92,215 + 1,871 (positive Obes) + 0.644 (serum sodium point) + 2,144 (glucose above normal) - 3,010 (low LDL) + 2,604 (high LDL).
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| Item Type: | Thesis (Doctor) |
|---|---|
| Identification Number: | DIS/615.71/WUL/p/2019/061901604 |
| Uncontrolled Keywords: | DRUGS AFFECTING CARDIOVASCULAR |
| Subjects: | 600 Technology (Applied sciences) > 615 Pharmacology and therapeutics > 615.7 Pharmacokinetics > 615.71 Drugs affecting cardiovascular and hematopoietic systems / Cardiovascular agents |
| Divisions: | S2/S3 > Doktor Ilmu Kedokteran, Fakultas Kedokteran |
| Depositing User: | Endang Susworini |
| Date Deposited: | 26 Jan 2022 07:47 |
| Last Modified: | 26 Jan 2022 07:47 |
| URI: | http://repository.ub.ac.id/id/eprint/188906 |
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