Srisawasdi Pornpen, Rodcharoen Punyanuch, Vanavanan Somlak, Chittamma Anchalee, Sukasem Chonlaphat, Na Nakorn Chalitpon, Dejthevaporn Charungthai, Kroll Martin H
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2021 Jan 6;14:1-13. doi: 10.2147/PGPM.S278671. eCollection 2021.
Patients treated with statins for dyslipidemia may still have a residual risk of atherosclerotic cardiovascular disease (ASCVD). To determine whether genetic variants in the cholesteryl ester transport protein (CETP), rs3764261 (C>A), rs708272 (G>A), and rs12149545 (G>A) affect ASCVD risk, we studied the association of these variants with dyslipidemia in statin-treated patients.
We included 299 adult Thai patients treated with a statin (95 men and 204 women). Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis. We used logistic regression models adjusted for potential confounders of age, body mass index, blood pressure, insulin resistance, and statin dosage to analyze the association between variants and atherogenic lipoprotein patterns.
polymorphisms of rs3764261 and rs708272, but not rs12149545, were significantly associated with high-density lipoprotein cholesterol (HDL-C), apoA-I, triglycerides, very low-density lipoprotein (VLDL)-C, and large LDL (LDL1-C) levels as well as mean LDL particle size (all < 0.020). However, no significant difference was observed in total cholesterol, LDL-C, or apoB levels by variants. Regardless of sex, the combination of rs3764261 (CC genotype) and rs708272 (GG or GA genotypes) showed a stronger association with atherogenic dyslipidemia, including features of decreased HDL-C, elevated triglycerides, and LDL subclass pattern B (odds ratio [OR] = 2.99, 95% confidence interval [CI]: 1.78-5.02) compared with the single variant rs3764261 (OR = 2.11, 95% CI: 1.27-3.50) or rs708272 (OR = 2.12, 95% CI: 1.29-3.49).
The polymorphisms of rs3764261 (CC genotype) and rs708272 (GG and GA genotypes) may have a higher susceptibility to atherogenic dyslipidemia. Testing for rs3764261 and rs708272 may serve as a surrogate marker for lipid management in statin-treated patients, which may help individualize treatment for reducing the residual risk of ASCVD.
接受他汀类药物治疗血脂异常的患者仍可能存在动脉粥样硬化性心血管疾病（ASCVD）的残余风险。为了确定胆固醇酯转运蛋白（CETP）基因变异rs3764261（C>A）、rs708272（G>A）和rs12149545（G>A）是否影响ASCVD风险，我们研究了这些变异与他汀类药物治疗患者血脂异常的相关性。
我们纳入了299例接受他汀类药物治疗的泰国成年患者（95名男性和204名女性）。通过基于TaqMan实时聚合酶链反应的分析进行基因分型。我们使用逻辑回归模型，对年龄、体重指数、血压、胰岛素抵抗和他汀类药物剂量等潜在混杂因素进行校正，以分析变异与致动脉粥样硬化脂蛋白模式之间的关联。
rs3764261和rs708272的多态性，而非rs12149545，与高密度脂蛋白胆固醇（HDL-C）、载脂蛋白A-I、甘油三酯、极低密度脂蛋白（VLDL）-C、大颗粒低密度脂蛋白（LDL1-C）水平以及平均LDL颗粒大小显著相关（均P<0.020）。然而，各变异在总胆固醇、LDL-C或载脂蛋白B水平上未观察到显著差异。无论性别如何，rs3764261（CC基因型）和rs708272（GG或GA基因型）的组合与致动脉粥样硬化性血脂异常的关联更强，包括HDL-C降低、甘油三酯升高和LDL亚类模式B等特征（比值比[OR]=2.99，95%置信区间[CI]：1.78-5.02），相比单个变异rs3764261（OR=2.11，95%CI：1.27-3.50）或rs708272（OR=2.12，95%CI：1.29-3.49）。
rs3764261（CC基因型）和rs708272（GG和GA基因型）的多态性可能对致动脉粥样硬化性血脂异常具有更高的易感性。检测rs3764261和rs708272可作为他汀类药物治疗患者血脂管理的替代标志物，这可能有助于个体化治疗以降低ASCVD的残余风险。
