Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions.
Enviado por Jose Gabriel Grajales Reyes el
Título | Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Autores | Grajales-Reyes, GE, Báez-Pagán, CA, Zhu, H, Grajales-Reyes, JG, Delgado-Vélez, M, García-Beltrán, WF, Luciano, CA, Quesada, O, Ramírez, R, Gómez, CM, Lasalde-Dominicci, JA |
Journal | Pharmacogenomics J |
Volume | 13 |
Issue | 4 |
Pagination | 362-8 |
Date Published | 2013 Aug |
ISSN | 1473-1150 |
Palabras clave | Alleles, Amino Acids, Animals, Caveolin 1, Cholesterol, Drug-Related Side Effects and Adverse Reactions, Gene Expression Regulation, Genome-Wide Association Study, Humans, Mice, Mice, Transgenic, Muscular Diseases, Polymorphism, Single Nucleotide, Receptors, Nicotinic |
Abstract | High cholesterol levels are an established risk factor for cardiovascular disease (CVD), the world's leading cause of death. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) are prescribed to lower serum cholesterol levels and reduce the risk of CVD. Despite the success of statins, many patients abandon treatment owing to neuromuscular adverse drug reactions (ADRs). Genome-wide association studies have identified the single-nucleotide polymorphism (SNP) rs4149056 in the SLCO1B1 gene as being associated with an increased risk for statin-induced ADRs. By studying slow-channel syndrome transgenic mouse models, we determined that statins trigger ADRs in mice expressing the mutant allele of the rs137852808 SNP in the nicotinic acetylcholine receptor (nAChR) α-subunit gene CHRNA1. Mice expressing this allele show a remarkable contamination of end-plates with caveolin-1 and develop early signs of neuromuscular degeneration upon statin treatment. This study demonstrates that genes coding for nAChR subunits may contain variants associated with statin-induced ADRs. |
DOI | 10.1038/tpj.2012.21 |
Alternate Journal | Pharmacogenomics J. |
PubMed ID | 22688219 |
PubMed Central ID | PMC3972001 |
Grant List | 2R01GM56371-12 / GM / NIGMS NIH HHS / United States R01 GM056371 / GM / NIGMS NIH HHS / United States R01 NS033202 / NS / NINDS NIH HHS / United States R01NS033202 / NS / NINDS NIH HHS / United States R25 GM061151 / GM / NIGMS NIH HHS / United States R25GM61151 / GM / NIGMS NIH HHS / United States T34 GM007821 / GM / NIGMS NIH HHS / United States T34GM007821 / GM / NIGMS NIH HHS / United States U54NS0430311 / NS / NINDS NIH HHS / United States |
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Enviado por Jose Gabriel Grajales Reyes el