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载脂蛋白 E 和载脂蛋白 A-V 的多态性不影响瑞舒伐他汀的血脂反应,但与中国高脂血症患者的基线血脂水平相关。

Polymorphisms in apolipoprotein E and apolipoprotein A-V do not influence the lipid response to rosuvastatin but are associated with baseline lipid levels in Chinese patients with hyperlipidemia.

机构信息

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

出版信息

J Clin Lipidol. 2012 Nov-Dec;6(6):585-92. doi: 10.1016/j.jacl.2012.02.005. Epub 2012 Feb 18.

Abstract

BACKGROUND

Apolipoprotein E (APOE) and APOA5 play an important role in lipid transport and metabolism. Polymorphisms in APOE and APOA5 have been reported to be associated with baseline lipid levels and lipid responses to statins in different populations.

OBJECTIVE

This study evaluated associations of APOE and APOA5 genotype with baseline lipid levels and response to rosuvastatin in Chinese patients with hyperlipidemia.

METHODS

A total of 386 patients with hyperlipidemia, including 166 with familial hypercholesterolemia (FH), with good adherence to rosuvastatin 10 mg daily, were genotyped for the APOE e2/e3/e4 and APOA5 -1131T>C polymorphisms. The lipid profile was examined before and after at least 4 weeks of therapy.

RESULTS

In patients without FH, there was a trend that e2 carriers had lower and those e4 carriers had higher low-density lipoprotein cholesterol (LDL-C) levels than subjects with the e3/e3 genotype (P > .05). However, an opposite significant association between APOE polymorphisms and LDL-C levels was observed in patients with FH (P = .005). The APOA5 -1131C variant allele was associated with increased baseline triglycerides levels in both patients with and without FH (P < .005 for both). Neither APOE nor APOA5 polymorphisms showed a significant effect on the lipid responses to rosuvastatin.

CONCLUSIONS

This study demonstrates different associations of APOE polymorphisms with baseline LDL-C concentrations in Chinese patients with or without FH and confirms the strong relation between the APOA5 polymorphism and baseline triglyceride levels. These findings expand our knowledge on the genetic determinants of lipids and lipid response to rosuvastatin in Chinese patients with hyperlipidemia.

摘要

背景

载脂蛋白 E(APOE)和载脂蛋白 A5 在脂质转运和代谢中发挥着重要作用。已有研究报道,APOE 和 APOA5 的多态性与不同人群的基线血脂水平以及对他汀类药物的血脂反应有关。

目的

本研究旨在评估 APOE 和 APOA5 基因型与中国高脂血症患者的基线血脂水平及对瑞舒伐他汀的反应之间的相关性。

方法

共纳入 386 例高脂血症患者,包括 166 例家族性高胆固醇血症(FH)患者,这些患者每天服用瑞舒伐他汀 10mg,依从性良好。对 APOE e2/e3/e4 和 APOA5 -1131T>C 多态性进行基因分型。在至少 4 周的治疗前后检查血脂谱。

结果

在无 FH 的患者中,e2 携带者的低密度脂蛋白胆固醇(LDL-C)水平较低,而 e4 携带者的 LDL-C 水平较高,与 e3/e3 基因型的受试者相比有升高趋势(P>.05)。然而,在 FH 患者中,APOE 多态性与 LDL-C 水平之间存在显著的相反关联(P=.005)。APOA5 -1131C 变异等位基因与无 FH 和有 FH 的患者的基线甘油三酯水平升高相关(两者均 P <.005)。APOE 或 APOA5 多态性均未对瑞舒伐他汀的血脂反应产生显著影响。

结论

本研究表明,APOE 多态性与中国 FH 患者和无 FH 患者的基线 LDL-C 浓度有不同的相关性,并证实了 APOA5 多态性与基线甘油三酯水平之间的强相关性。这些发现扩展了我们对中国高脂血症患者血脂和瑞舒伐他汀血脂反应的遗传决定因素的认识。

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