Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia
Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia
复制标题
DOI：
10.1016/j.atherosclerosis.2011.08.015
复制
发表时间：
2011-12-01
期刊：
影响因子：
5.3
通讯作者：
Ballantyne, Christie M.
中科院分区：
文献类型：
--
作者：
Brautbar, Ariel;Covarrubias, Daniel;Ballantyne, Christie M.
目的：致动脉粥样硬化性血脂异常与冠心病高度相关，其特点是甘油三酯（TG）升高、高密度脂蛋白胆固醇（HDL-C）降低和低密度脂蛋白胆固醇（LDL-C）升高。他汀类药物和贝特类药物联合治疗是治疗动脉粥样硬化性血脂异常患者的常见方法。我们试图鉴定与他汀类药物和非诺贝酸 (FA) 联合治疗对动脉粥样硬化性血脂异常患者的 HDL-C、TG 和载脂蛋白 A1 (ApoA-I) 反应相关的单核苷酸多态性 (SNP)。方法：2228 名患有混合性血脂异常的患者参加了一项研究。多中心、随机、双盲、主动对照研究比较了单独使用 FA、联合他汀类药物或单独使用他汀类药物 12 周，对 304 个候选 SNP 进行了基因分型。对 HDL-C、ApoA-I 和 TG 水平变化百分比进行多元线性回归分析。结果：载脂蛋白 (APO) A5-ZNF259 区域 rs3741298 (P = 1.8 x 10(-7))、rs964184 (P=3.6 x 10(-6))、rs651821 (P=4.5) 中的 SNP x 10(-5)) 和 rs10750097 (P=1 x 10(-4)) 与 HDL-C 对他汀类药物和 FA 联合治疗的反应显着相关，ApoA-I 也有类似的相关性。由 SNP rs3741298、rs964184 和 rs10750097 的次要等位基因组成的单倍型与他汀类药物和 FA 的阳性反应相关 (P = 8.7 x 10(-7))，并且在研究人群中的频率为 18%。结论：在患有动脉粥样硬化性血脂异常的人群中，常见的 SNP 和单倍型在AP0A5-ZNF259 区域与 HDL-C 和 ApoA-I 对他汀类药物和 FA 联合治疗的反应高度相关。 (C) 2011 年，爱思唯尔爱尔兰有限公司出版。
Objective: Atherogenic dyslipidemia is highly associated with coronary heart disease and is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol (LDL-C). The combination of statins and fibrates is a common modality to treat individuals with atherogenic dyslipidemia.We sought to identify single nucleotide polymorphisms (SNPs) associated with HDL-C, TG, and apolipoprotein A1 (ApoA-I) response to combination therapy with statins and fenofibric acid (FA) in individuals with atherogenic dyslipidemia.Methods: 2228 individuals with mixed dyslipidemia who were participating in a multicenter, randomized, double-blind, active-controlled study comparing FA alone, in combination with a statin, or statin alone for a 12-week period, were genotyped for 304 candidate SNPs. A multivariate linear regression analysis for percent change in HDL-C, ApoA-I and TG levels was performed.Results: SNPs in the apolipoprotein (APO) A5-ZNF259 region rs3741298 (P = 1.8 x 10(-7)), rs964184 (P=3.6 x 10(-6)), rs651821 (P=4.5 x 10(-5)), and rs10750097 (P=1 x 10(-4)), were significantly associated with HDL-C response to combination therapy with statins and FA, with a similar association identified for ApoA-I. A haplotype composed of the minor alleles of SNPs rs3741298, rs964184, and rs10750097, was associated with a positive response to statins and FA (P = 8.7 x 10(-7)) and had a frequency of 18% in the study population.Conclusion: In a population with atherogenic dyslipidemia, common SNPs and haplotypes within the AP0A5-ZNF259 region are highly associated with HDL-C and ApoA-I response to combination therapy with statins and FA. (C) 2011 Published by Elsevier Ireland Ltd.