Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner
Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner
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DOI：
10.1016/s0021-9150(01)00410-5
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发表时间：
2001-09-01
期刊：
影响因子：
5.3
通讯作者：
Ordovas, JM
中科院分区：
文献类型：
--
作者：
Pedro-Botet, J;Schaefer, EJ;Ordovas, JM
对降血脂药物治疗的反应显示出相当大的个体差异。这些差异可能是由于影响药物生物利用度、受体功能或配体结构的环境和遗传因素的相互作用造成的。我们的目的是评估载脂蛋白 (apo) E 基因型和性别对 HMG CoA 还原酶抑制剂阿托伐他汀降脂反应的影响。对 328 名男性和女性受试者的 DNA 进行了基因分型，这些受试者参加了一项多中心、双盲临床试验，并每天接受 10 毫克阿托伐他汀治疗。我们的数据表明，基线 LDL 胆固醇水平没有显着的性别差异。此外，与基线相比，男性（- 36.2%，范围 - 2.7 至 - 57.8%）和女性（-38.1%，范围 9.5 至 -58.5%）的平均 LDL-C 降低相似。然而，携带 epsilon2 等位基因的男性平均 LDL-C 反应 (-44%) 显着高于 epsilon3 纯合子 (-37%) 和 epsilon4 携带者 (-34%)；根据治疗相互作用，apoE 组 P = 0.01。在女性中没有发现这种基因/治疗相互作用，携带 epsilon2 等位基因的女性显示出与 epsilon3 纯合子 (-39%) 和 epsilon4 携带者 (-34%) 相似的平均反应 (-34%)。阿托伐他汀使血浆甘油三酯平均降低 17%。在男性中也观察到治疗相互作用显着的 apoE 组 (P = 0.010)，e2 携带者的反应性 (-27%) 比 epsilon3/3 (-13%) 和 epsilon4 (-22%) 更高。在女性中没有观察到这种相互作用。总之，阿托伐他汀治疗对男性和女性的血脂水平具有相似的影响。然而，apoE 基因位点是男性 LDL-C 和 TG 对阿托伐他汀治疗反应的重要预测因子，但在女性中则不然。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (- 36.2%, range - 2.7 to - 57.8%) and in women (-38.1%, range 9.5 to -58.5%) as compared to baseline. However, men carrying the epsilon2 allele had a significantly higher mean LDL-C response (-44%) than epsilon3 homozygotes (-37%) and epsilon4 carriers (-34%); P = 0.01 for apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the epsilon2 allele showing a similar mean response (-34%) as epsilon3 homozygotes (-39%) and epsilon4 carriers ( -34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant apoE group by treatment interaction (P = 0.010) was also observed in men, with e2 carriers being more responsive (-27%) than epsilon3/3 ( -13%) and epsilon4 (-22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.