The role of HMGCR alternative splicing in statin efficacy.
The role of HMGCR alternative splicing in statin efficacy.
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DOI：
10.1016/j.tcm.2009.10.003
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发表时间：
2009-07
影响因子：
9.3
通讯作者：
Krauss, Ronald M.
中科院分区：
文献类型：
--
作者：
Medina, Marisa Wong;Krauss, Ronald M.
他汀类药物，或3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）抑制剂，被广泛用于降低血浆胆固醇水平和降低心血管疾病（CVD）风险。尽管他汀类药物的疗效有充分的证据，但个体间的反应差异很大。使用一组与辛伐他汀孵育的永生化淋巴细胞系，我们最近发现，缺乏外显子13的选择性剪接HMGCR转录物的表达幅度与他汀类药物治疗后细胞来源的个体体内总胆固醇、LDL胆固醇、载脂蛋白B和甘油三酯的降低呈负相关。这篇综述将讨论选择性剪接作为一种机制的潜在意义，有助于他汀类药物疗效的变化，以及利用永生化淋巴细胞系识别药物遗传学相关的多态性和分子机制。
Statins, or 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, are widely prescribed to lower plasma cholesterol levels and reduce cardiovascular disease (CVD) risk. Despite the well documented efficacy of statins, there is large inter-individual variation in response. Using a panel of immortalized lymphocyte cell lines incubated with simvastatin, we recently found that the magnitude of expression of an alternatively spliced HMGCR transcript lacking exon 13 was inversely correlated with in vivo reductions of total cholesterol, LDL cholesterol, apoB, and triglycerides following statin treatment of the individuals from whom the cells were derived. This review will discuss the potential significance of alternative splicing as a mechanism contributing to variation in statin efficacy as well as the utility of immortalized lymphocyte cell lines for identifying pharmacogenetically relevant polymorphisms and molecular mechanisms.
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影响因子：
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