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中国患者对瑞舒伐他汀的血脂反应的遗传药理学分析。

Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.

机构信息

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

出版信息

Pharmacogenet Genomics. 2010 Oct;20(10):634-7. doi: 10.1097/FPC.0b013e32833de489.

Abstract

Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.

摘要

由于目前尚不清楚具体原因,他汀类药物治疗引起的脂类变化在个体之间存在很大差异。本研究旨在探讨中国患者对瑞舒伐他汀的脂质反应的遗传决定因素。对 386 例中国患者的 61 个候选基因中的 125 个多态性与瑞舒伐他汀 10mg/d 的脂质反应进行了关联分析。与低密度脂蛋白胆固醇(LDL-C)反应相关性最强的多态性是 ATP 结合盒 G2 基因中的 421C>A(P=9.2×10),其次是黄素单氧化酶 3 基因中的 18281G>A(V257M)(P=0.0002),脂蛋白脂肪酶基因中的 1421C>G(P=0.002)和载脂蛋白 E/C-I/C-IV/C-II 基因簇中的 rs4420638(P=0.004)。家族性高胆固醇血症患者的 LDL-C 降低幅度比非家族性高胆固醇血症患者小 2.6%。本研究确定了中国患者对瑞舒伐他汀的 LDL-C 反应的一些遗传决定因素,这些因素需要在其他人群中得到验证。

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