Mangravite Lara M, Krauss Ronald M
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
Curr Opin Lipidol. 2007 Aug;18(4):409-14. doi: 10.1097/MOL.0b013e328235a5a2.
Although statin therapy has been shown to reduce substantially the risk for cardiovascular disease in multiple patient subgroups, there is wide inter-individual variation in statin efficacy, in terms of both plasma lipoprotein response and clinical outcome.
A number of studies have reported that polymorphisms in genes affecting statin pharmacodynamics and pharmacokinetics are associated with measures of statin efficacy, but the magnitude of variation in statin response that could be explained by these associations is small. Genome-wide association studies may yield a more comprehensive set of markers for predicting statin efficacy and muscle toxicity. For the results of these analyses to have clinical value, however, there remains a need to replicate findings in multiple populations, to connect effects on LDL and other biomarkers with clinical outcomes, and to determine whether the associations apply to each individual statin.
Satisfying these requirements for clinical applicability will be challenging, but discovery of specific genotypes that influence statin efficacy and characterization of their functional effects in cellular or animal model systems may enhance our understanding of determinants of cardiovascular disease risk. They may also allow us to identify pathways that may be targeted to yield effective prevention and treatment.
尽管他汀类药物治疗已被证明可在多个患者亚组中大幅降低心血管疾病风险，但在他汀类药物疗效方面，无论是血浆脂蛋白反应还是临床结局，个体间都存在很大差异。
多项研究报告称，影响他汀类药物药效学和药代动力学的基因多态性与他汀类药物疗效指标相关，但这些关联所能解释的他汀类药物反应变异程度较小。全基因组关联研究可能会产生一套更全面的预测他汀类药物疗效和肌肉毒性的标志物。然而，要使这些分析结果具有临床价值，仍需要在多个群体中重复研究结果，将对低密度脂蛋白和其他生物标志物的影响与临床结局联系起来，并确定这些关联是否适用于每种他汀类药物。
满足这些临床适用性要求将具有挑战性，但发现影响他汀类药物疗效的特定基因型并在细胞或动物模型系统中表征其功能效应，可能会增进我们对心血管疾病风险决定因素的理解。它们还可能使我们识别出可作为靶点以实现有效预防和治疗的途径。
