Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy
Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy
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DOI：
10.2217/14622416.9.9.1217
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发表时间：
2008-09-01
期刊：
影响因子：
2.1
通讯作者：
Carrie, Alain
中科院分区：
文献类型：
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作者：
Couvert, Philippe;Giral, Philippe;Carrie, Alain
简介：低密度脂蛋白胆固醇（LDL-C）水平显著降低（G，c.463C>A和c.521T>C）。结果：由于连锁不平衡，SLCO 1B 1除了野生型等位基因（*1a）外，仅检测到4个等位基因（*1b，*5，*14和 *15）。与对应于 *14等位基因的c.388G SNP系统性相关的c.463A基因型与LDL-C较基线的降低百分比（p = 0.005）和平均治疗后LDL-C值（p = 0.0005）显著相关。与杂合子C/A患者（-36.2%，126 mg/dl; n = 111）和纯合子A/A受试者（-41%，115 mg/dl; n = 15）相比，c.463C基因型纯合子受试者（n = 294）表现出显著更低的LDL-C降低和更高的治疗后LDL-C水平（-31.5%，138 mg/dl）。结论：这些结果表明OATP 1B 1与氟伐他汀的药理作用和疗效有关。事实上，在这项研究中，共同的 *14等位基因（以c.463C>A多态性的存在为特征）与增强的降脂功效相关。
Introduction: Marked lowering of low-density-lipoprotein cholesterol (LDL-C) levels (G, c.463C>A and c.521T>C). Results: Due to linkage disequilibrium, only four alleles (*1b, *5, *14 and *15) of SLCO1B1 were detected in addition to the wild-type allele (*1a). The c.463A genotype, which was systematically associated with the c.388G SNP corresponding to the *14 allele was significantly associated with percentage LDL-C reduction from baseline (p = 0.005) and with mean post-treatment LDL-C values (p = 0.0005). Subjects homozygous for the c.463C genotype (n = 294) exhibited significantly less LDL-C reduction and higher post-treatment LDL-C levels (-31.5%, 138 mg/dl) relative to heterozygous C/A patients (-36.2%, 126 mg/dl; n = 111), and to homozygous A/A subjects (-41%, 115 mg/dl; n = 15). Conclusions: These results reveal that OATP1B1 is implicated in the pharmacological action and efficacy of fluvastatin. Indeed, the common *14 allele, which is distinguished by the presence of the c.463C>A polymorphism, was associated with enhanced lipid-lowering efficacy in this study.