Suprapti, Herni (2019) Perbedaan Polimorfisme Gen Slco1b1*5 (Snp Rs4149056t>C) Dan Gen Cyp3a4*22 Pada Efikasi Simvastatin Yang Dilihat Dari Perubahan Cimt, Fmd, Dan Abi Sebagai Marker Terjadinya Aterosklerosis Subklinis Pada Suku Jawa. Doctor thesis, Universitas Brawijaya.
Abstract
Aterosklerosis merupakan penyebab kematian hampir separuh orang berusia lebih dari 60 tahun di seluruh dunia. Simvastatin banyak digunakan, well-tolerated, dan efektif untuk menurunkan kolesterol LDL (low-density lipoprotein) dan menurunkan risiko serangan jantung. Statin dapat menurunkan kolesterol LDL sekitar ∼40%, dan semakin besar penurunan kolesterol LDL akan makin besar juga penurunan risiko serangan jantung. Respons lipid terhadap statin dipengaruhi berbagai hal, termasuk faktor genetik, tetapi data interaksi farmakogenetik dan pengaruhnya pada risiko respons terhadap statin masih sangat terbatas. Masih belum jelas apakah variasi genetik menyebabkan perbedaan efek terapi statin dan mempengaruhi keadaan klinis pasien. Polimorfisme pada gen transporter obat dan/atau gen enzim metabolisme obat, berkontribusi pada variabilitas inter-individual pada farmakokinetik simvastatin. Carotid intima-media thickness (CIMT), FMD (Flow Mediated Dilation), dan Ankle-Brachial Index (ABI), merupakan marker untuk aterosklerosis subklinis. Penelitian ini bertujuan untuk menemukan polimorfisme gen SLCO1B1*5 (snp rs4149056T>C) dan gen CYP3A4*22 pada pasien kardiovaskuler suku Jawa yang diberi terapi Simvastatin untuk mencegah terjadinya aterosklerosis akibat dislipidemia. Selain itu untuk mengetahui perbedaan efek polimorfisme gen SLCO1B1*5 (snp rs4149056T>C) dan gen CYP3A4*22 pada efikasi simvastatin yang dilihat dari perubahan cimt, fmd, dan abi, serta perbedaan polimorfisme gen SLCO1B1 dengan profil lipid (Kolesterol total, LDL, HDL, Rasio Kolesterol Total/HDL, dan TG) dan faktor risiko aterosklerosis dini (Tekanan darah sistolik dan kebiasaan merokok). Studi deskriptif potong-lintang dilakukan di laboratorium genetika FK UWKS, sejak Januari 2016 sampai Desember 2017. Studi komparatif dilakukan untuk membandingkan polimorfisme gen SLCO1B1 dengan Marker aterosklerosis dini (CIMT, FMD, dan ABI), profil lipid (Kolesterol total, LDL, HDL, Rasio Kolesterol Total/HDL, dan TG), faktor risiko aterosklerosis dini (Tekanan darah sistolik dan kebiasaan merokok), dan karakteristik subyek penelitian (jenis kelamin,usia, BMI, durasi simvastatin). Delapan puluh tiga subjek penelitian pasien kardiovaskuler yang diberi terapi simvastatin minimal selama 3 bulan, direkrut dalam penelitian ini. Hasil analisis gen SLCO1B1*5 (snp rs4149056T>C) menunjukkan sebanyak 89% berupa alel homozygot TT (wild-type), 11% alel heterozygot TC (mutant-type), dan tidak didapatkan alel homozygot CC (0%). Persentase alel C 4,8%. Sedangkan hasil analisis gen CYP3A4*22 semua berupa alel homozygot TT (100%), tidak didapatkan alel heterozygot TC (0%) maupun homozygot TT (0%). Didapatkan perbedaan bermakna (p=0,000) alel homozygot TT dengan alel heterozygot TC pada Marker aterosklerosis dini (CIMT, FMD, dan ABI), profil lipid (Kolesterol total, LDL, HDL, Rasio Kolesterol Total/HDL, dan TG), faktor risiko aterosklerosis dini (Tekanan darah sistolik dan kebiasaan merokok), dan karakteristik subyek penelitian (jenis kelamin, usia, BMI, durasi simvastatin). Kesimpulan: Didapatkan adanya polimorfisme gen SLCO1B1 (snp rs4149056T>C) alel heterozygot TC sebanyak 11% pada suku Jawa. Adanya alel C menyebabkan perbedaan pada marker aterosklerosis dini (CIMT, FMD, dan ABI), profil lipid (Kolesterol total, LDL, HDL, Rasio Kolesterol Total/HDL, dan TG), faktor risiko aterosklerosis dini (Tekanan darah sistolik dan kebiasaan merokok), dan karakteristik subyek penelitian (jenis kelamin,usia, BMI, durasi simvastatin).
English Abstract
Atherosclerosis is a cause of death that has been separated for more than 60 years worldwide. Simvastatin is widely used, well tolerated, and effective for lowering LDL (low-density lipoprotein) cholesterol and reducing the risk of heart attack. Statins can reduce LDL cholesterol by about ∼40%, and the greater the decrease in LDL cholesterol, the greater the risk of heart attack. Lipid responses to statins determine various things, including genetic factors, but data on pharmacogenetic interactions and their effects on responses to statins are still very limited. It is still unclear whether genetic variation causes differences in the effects of statins and affects the patient's clinical condition. Polymorphism in the transporter gene and / or enzyme gene contributing drugs, contributes to the variability between individuals in the pharmacokinetics of simvastatin. Carotid intima-media thickness (CIMT), FMD (Flow Mediated Dilation), and Ankle-Brachial Index (ABI), are markers for subclinical atherosclerosis. This study aims to find the SLCO1B1 (snp rs4149056T> C) gene and CYP3A4 gene polymorphism in Javanese cardiovascular patients who offer Simvastatin therapy to replace atherosclerosis due to dyslipidemia. In addition to see the effect on the SLCO1B1*5 (snp rs4149056T>C) gene polymorphism and CYP3A4*22 gene on the efficacy of simvastatin associated with CIMT, FMD, and ABI, as well as the SLCO1B1 gene polymorphism with lipid profiles (total cholesterol, LDL, HDL, total cholesterol/HDL ratio, and TG) and risk factors for early atherosclerosis (systolic blood pressure and smoking habits). Cross-sectional descriptive studies were carried out in the FK UWKS genetic laboratory from January 2016 to December 2017. A comparative study was conducted to compare the SLCO1B1 gene polymorphism with early atherosclerosis markers (CIMT, FMD, and ABI), lipid profiles (total cholesterol, LDL, HDL, Total cholesterol / HDL ratio, and TG), risk factors for early atherosclerosis, and characteristics of the study subjects (gender, age, BMI, duration of simvastatin). Eighty-three subjects of cardiovascular patients who were given simvastatin therapy for at least 3 months were recruited in this study. The results of the SLCO1B1*5 (snp rs4149056T>C) gene analysis showed that 89% consisted of homozygot TT alleles (wild type), 11% TC heterozygot alleles (mutant type), and no homozygot CC alleles (0%). Percentage of C allele 4.8%. While the results of the CYP3A4*22 gene analysis all consisted of a homozygot TT allele (100%), not obtained heterozygot TC alleles (0%) or TT homozygots (0%). Significant differences (p = 0,000) homozygot allele TT with heterozygot TC alleles in early atherosclerosis markers (CIMT, FMD, and ABI), lipid profiles (total cholesterol, LDL, HDL, Total cholesterol ratio / HDL, and TG), early atherosclerosis and the characteristics of the research subjects (gender, age, BMI, duration of simvastatin). Conclusion: There were 11% SLCO1B1 (snp rs4149056T> C) gene polymorphisms in TC heterozygot alleles in the Javanese. The presence of the C allele causes differences in the markers of early atherosclerosis (CIMT, FMD, and ABI), lipid profiles (total cholesterol, LDL, HDL, ratio of total cholesterol / HDL, and TG), risk factors for early atherosclerosis (systolic pressure and waiting), and characteristics of the research subjects (gender, age, BMI, duration of simvastatin).
Other obstract
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| Item Type: | Thesis (Doctor) |
|---|---|
| Identification Number: | DIS/615.71/SUP/p/2019/061910518 |
| Uncontrolled Keywords: | SLCO1B1*5, CYP3A4*22, Simvastatin, CIMT, FMD, ABI, Suku Jawa,-SLCO1B1*5, CYP3A4*22, Simvastatin, CIMT, FMD, ABI, Javanese |
| 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: | 11 Feb 2022 07:34 |
| Last Modified: | 11 Feb 2022 07:34 |
| URI: | http://repository.ub.ac.id/id/eprint/189730 |
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