Clinical implications of pharmacogenomics of statin treatment

Role of Micro-RNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

“…Among them, statins are recognized as the main cholesterol-lowering drugs by reducing the cholesterol contents through the inhibition of the 3-hydroxy-3-methyl-glutaryl coA reductase (HMGCR), an enzyme with a key function in the endogenous biosynthesis of the cholesterol 7 . On the other hand, ezetimibe also reduces cholesterol contents by interacting with the Niemann-Pick C1-like 1 (NPC1L1), which results in a decreased cholesterol absorption 8 .…”

APOE gene polymorphisms and response to statin therapy

“…1 However, considerable interindividual variation exists in response to statin therapy, in terms of lipid responses or clinical outcomes. 2,3 Important factors in interpreting this variability include the patient's overall health, prognosis, disease severity, quality of drug prescribing, compliance with prescribed pharmacotherapy and the genetic profile of the patient. 4 The search for genetic determinants of treatmenteffect heterogeneity has included more than 40 different genes involved in the pharmacokinetic and pharmacodynamic pathways of statin metabolism.…”

“…4 The search for genetic determinants of treatmenteffect heterogeneity has included more than 40 different genes involved in the pharmacokinetic and pharmacodynamic pathways of statin metabolism. 2,3 Among the most extensively studied pharmacodynamic genes is the APOE gene, encoding Apolipoprotein E. Apo E is a constituent of triglyceride-rich chylomicrons, very low-density lipoprotein particles, intermediate-density lipoproteins and a subclass of high-density lipoprotein cholesterol (HDL-C). Three major Apolipoprotein E isoforms are coded by three alleles at the APOE gene, designated as e2, e3 and e4 (dbSNP accession numbers, rs7412 and rs429358).…”

“…Differential interpretation of these results among investigators has led to the publication of contradictory consensus statements regarding the role of e2 and e4 alleles in determination of statin effect. 2,3 By considering all available studies in a metaanalysis, our study aims to decrease the uncertainty of the estimated effect size of APOE genetic variants on lipid response to statin treatment and to provide more conclusive evidence regarding the clinical relevance of this proposed pharmacogenetic association.…”

Efeitos de hipolipemiantes sobre a expressão de CYP3A4 e CYP3A5 in vitro e in vivo

“…A CYP2C8 participa somente do metabolismo da sinvastatina, convertendo a forma ácida de sinvastatina a seus metabólitos (Figura 2). (MANGRAVITE; THORN; KRAUSS, 2006). A especificidade bioquímica de CYP3A4 e CYP3A5 pelos seus substratos é tão semelhante que são dificilmente distinguidas (WILKINSON, 2005).…”