Vanwong Natchaya, Tipnoppanon Sayanit, Na Nakorn Chalitpon, Srisawasdi Pornpen, Rodcharoen Punyanuch, Medhasi Sadeep, Chariyavilaskul Pajaree, Siwamogsatham Sarawut, Vorasettakarnkij Yongkasem, Sukasem Chonlaphat
Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Cardiovascular Precision Medicine Research Group, Special Task Force of Activating Research (STAR), Chulalongkorn University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2022 Feb 17;15:119-130. doi: 10.2147/PGPM.S346093. eCollection 2022.
Statins are increasingly widely used in the primary and secondary prevention of cardiovascular disease. However, there is an inter-individual variation in statin response among patients. The study aims to determine the association between genetic variations in drug-metabolizing enzyme and transporter (DMET) genes and lipid-lowering response to a statin in Thai patients with hyperlipidemia.
Seventy-nine patients who received statin at steady-state concentrations were recruited. Serum lipid profile was measured at baseline and repeated after 4-month on a statin regimen. The genotype profile of 1936 DMET markers was obtained using Affymetrix DMET Plus genotyping microarrays.
In this DMET microarray platform, five variants; (rs4149117, rs7311358, and rs2053098), (rs13331798), and (rs188096) showed a suggestive association with LDL-cholesterol-lowering response. HDL-cholesterol-lowering responses were found to be related to gene variant (rs12542233). Seven variants, (rs4149117, rs7311358, and rs2053098); (rs3736599 and rs3822172); and (rs4148768 and rs3770603), were associated with the total cholesterol-lowering response. One variant of the gene (rs2109505) was significantly associated with triglyceride-lowering response.
This pharmacogenomic study identifies new genetic variants of DMET genes that are associated with the lipid-lowering response to statins. Genetic polymorphisms in DMET genes may impact the pharmacokinetics and lipid-lowering response to statin. The validation studies confirmations are needed in future pharmacogenomic studies.
他汀类药物在心血管疾病的一级和二级预防中应用越来越广泛。然而，患者对他汀类药物的反应存在个体差异。本研究旨在确定泰国高脂血症患者中药物代谢酶和转运体（DMET）基因的遗传变异与他汀类药物降脂反应之间的关联。
招募了79例接受稳态浓度他汀类药物治疗的患者。在基线时测量血脂谱，并在接受他汀类药物治疗4个月后重复测量。使用Affymetrix DMET Plus基因分型微阵列获得1936个DMET标记的基因型谱。
在这个DMET微阵列平台上，五个变异体（rs4149117、rs7311358和rs2053098）、（rs13331798）和（rs188096）显示出与低密度脂蛋白胆固醇降低反应存在提示性关联。发现高密度脂蛋白胆固醇降低反应与基因变异体（rs12542233）有关。七个变异体（rs4149117、rs7311358和rs2053098）、（rs3736599和rs3822172）以及（rs4148768和rs3770603）与总胆固醇降低反应有关。基因（rs2109505）的一个变异体与甘油三酯降低反应显著相关。
这项药物基因组学研究确定了与他汀类药物降脂反应相关的DMET基因新的遗传变异体。DMET基因的遗传多态性可能影响他汀类药物的药代动力学和降脂反应。未来的药物基因组学研究需要进行验证性研究。
