lunes, 12 de mayo de 2014

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review : Genetics in Medicine : Nature Publishing Group

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review : Genetics in Medicine : Nature Publishing Group



Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

Genetics in Medicine
 
(2014)
 
doi:10.1038/gim.2014.41
Received
 
Accepted
 
Published online 

Abstract

Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6,CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review:CYP2D6CYP3A4CYP3A5GATMSLCO1B1ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.
Genet Med advance online publication 8 May 2014

Keywords:

 
muscle toxicity; myopathy; pharmacogenomics; SLCO1B1; statins

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