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Jaroslav A Hubáček, Dana Dlouhá, Vera Adámková, Lukáš Zlatohlavek, Ondřej Viklický, Petra Hrubá, Richard Češka, Michal Vrablík
BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed...
May 20, 2015: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jacqueline S Danik, Daniel I Chasman, Jean G MacFadyen, Fredrik Nyberg, Bryan J Barratt, Paul M Ridker
BACKGROUND: Carriers of the rs4363657C and rs4149056C alleles in SLCO1B1 have increased myopathic complaints when taking simvastatin. Whether rosuvastatin has a similar effect is uncertain. This study assesses whether SLCO1B1 polymorphisms relate to clinical myalgia after rosuvastatin therapy. METHODS: In the JUPITER trial, participants without prior cardiovascular disease or diabetes who had low-density lipoprotein cholesterol <130 mg/dL and C-reactive protein ≥2 mg/L were randomly allocated to rosuvastatin 20 mg or placebo and followed for the first cardiovascular disease events and adverse effects...
June 2013: American Heart Journal
M Francesca Notarangelo, N Marziliano, M Antonietta Demola, F Pigazzani, A Guidorossi, P Angelica Merlini, D Ardissino
WHAT IS KNOWN AND OBJECTIVE: The major clinical complication of statins is a variety of muscle complaints ranging from myalgia to rhabdomyolysis. There is growing evidence that carriers of genetic polymorphisms in the enzymes and transporters implicated in statin disposition, particularly the SLCO1B1 gene, are at increased risk of myotoxicity. Our objective is to report on two cases of statin-induced myopathy occurring in a family with two patients who are carriers of the loss of function SLCO1B1 genetic variant and to briefly review the related literature...
October 2012: Journal of Clinical Pharmacy and Therapeutics
Paulo C J L Santos, Renata A G Soares, Raimundo M Nascimento, George L L Machado-Coelho, José G Mill, José E Krieger, Alexandre C Pereira
BACKGROUND: Recent studies reported the association between SLCO1B1 polymorphisms and the development of statin-induced myopathy. In the scenario of the Brazilian population, being one of the most heterogeneous in the world, the main aim here was to evaluate SLCO1B1 polymorphisms according to ethnic groups as an initial step for future pharmacogenetic studies. METHODS: One hundred and eighty-two Amerindians plus 1,032 subjects from the general urban population were included...
October 12, 2011: BMC Medical Genetics
Suzette J Bielinski, High Seng Chai, Jyotishman Pathak, Jayant A Talwalkar, Paul J Limburg, Rachel E Gullerud, Hugues Sicotte, Eric W Klee, Jason L Ross, Jean-Pierre A Kocher, Iftikhar J Kullo, John A Heit, Gloria M Petersen, Mariza de Andrade, Christopher G Chute
OBJECTIVE: To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with high-throughput genetic data and electronic medical record (EMR) data for phenotype extraction. PARTICIPANTS AND METHODS: Eligible participants include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators...
July 2011: Mayo Clinic Proceedings
Gregory Dendramis
The enzyme HMG-CoA reductase (HMGCR), the main site of action of statins, undergoes alternative splicing of exon 13, which encodes the binding domain of statins to the enzyme. The resulting isoform, called HMGCRv1, shows altered enzyme activity and sensitivity to statins compared to the classical isoform. This translates into interindividual differences in the response to treatment with these drugs. A recent discovery in the field of genetics has brought about the identification of the single nucleotide polymorphism rs4363657 of the SLCO1B1 gene located on chromosome 12...
March 2011: Giornale Italiano di Cardiologia
E Link, S Parish, J Armitage, L Bowman, S Heath, F Matsuda, I Gut, M Lathrop, R Collins
BACKGROUND: Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. METHODS: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants...
August 21, 2008: New England Journal of Medicine
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