School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, Thailand.
Department of Medicine, Hatyai Hospital, Songkhla, Thailand.
Cardiovasc Ther. 2017 Dec;35(6). doi: 10.1111/1755-5922.12302. Epub 2017 Sep 25.
To investigate the effect of apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and proprotein convertase subtilisin kexin type 9 (PCSK9) polymorphisms on the lipid-lowering response to simvastatin therapy in Thai hypercholesterolemic patients.
Two hundred and twenty-five hypercholesterolemic patients in southern Thailand were enrolled and treated with simvastatin 20 or 40 mg per day for 3 months. Serum lipids were measured before and after the therapy. APOE, CETP TaqIB, and PCSK9 (R46L, I474V, and E670G) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
After 3 months of simvastatin therapy, subjects with APOE2 (Total cholesterol [TC]: -30.89% vs-13.56%, P < .05, LDL-C: -45.00% vs -17.73%, P < .05) and APOE3 carriers (TC: -26.22% vs -13.56%, P < .05, LDL-C: -37.14% vs -17.73%, P < .05) had greater TC and LDL-C reduction compared to APOE4 carriers, whereas CETP TaqIB B2B2 genotype showed lower TC (-16.37% vs -24.92%, P = .016) and LDL-C (-22.54% vs -35.19%, P = .028) reduction compared to CETP TaqIB B1 carriers. In addition, PCSK9 474IV carriers showed greater LDL-C (-50.57% vs -32.99%) reduction compared to PCSK9 474II carriers. Combined effect analyses showed that individuals carrying more risk alleles tended to have lower TC and LDL-C (P for trend = .000 and .000, respectively) reduction in response to simvastatin therapy.
APOE4 carriers and the CETP TaqIB B2B2 genotype were associated with a decreased response, but PCSK9 474IV carriers tended to be associated with an increased response to simvastatin therapy in Thai hypercholesterolemic patients.
研究载脂蛋白 E (APOE)、胆固醇酯转移蛋白 (CETP) 和前蛋白转化酶枯草溶菌素 9 (PCSK9) 多态性对泰国高胆固醇血症患者辛伐他汀治疗降脂反应的影响。
在泰国南部招募了 225 名高胆固醇血症患者，每天服用辛伐他汀 20 或 40mg，治疗 3 个月。治疗前后测定血清脂质。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析 APOE、CETP TaqIB 和 PCSK9（R46L、I474V 和 E670G）多态性。
辛伐他汀治疗 3 个月后，APOE2 携带者（TC：-30.89%比-13.56%，P<.05，LDL-C：-45.00%比-17.73%，P<.05）和 APOE3 携带者（TC：-26.22%比-13.56%，P<.05，LDL-C：-37.14%比-17.73%，P<.05）的 TC 和 LDL-C 降低幅度大于 APOE4 携带者，而 CETP TaqIB B2B2 基因型的 TC（-16.37%比-24.92%，P=.016）和 LDL-C（-22.54%比-35.19%，P=.028）降低幅度大于 CETP TaqIB B1 携带者。此外，PCSK9 474IV 携带者的 LDL-C 降低幅度更大（-50.57%比-32.99%）。联合效应分析表明，携带更多风险等位基因的个体在辛伐他汀治疗中的 TC 和 LDL-C 降低幅度较低（P 趋势值=0.000 和 0.000）。
APOE4 携带者和 CETP TaqIB B2B2 基因型与辛伐他汀治疗反应降低相关，但 PCSK9 474IV 携带者与泰国高胆固醇血症患者对辛伐他汀治疗的反应增加相关。
