The study showed that a SNP

in SLCO1B1, which encodes the organic anion-transporting polypeptide OATP1B1, was very strongly associated with statin-induced myopathy.1 Each copy of the variant allele conferred an odds ratio of 4.5. The odds ratio was 16.9 for homozygotes relative to the non-risk genotype. It was estimated that carriers of the variant allele accounted for 60% of all statin-induced myopathy cases. While the association with simvastatin-induced myopathy has been confirmed, it is not evident among individuals prescribed atorvastatin or pravastatin.46 The Pharmacogenomics of Beta-Blockers Inhibitors,research,lifescience,medical Beta-blocker pharmacogenomics has focused on polymorphisms in both the beta-1 and beta-2 receptors (ADRB1 Inhibitors,research,lifescience,medical and ADRB2), angiotensin-converting enzyme, and cytochrome P450 2D6.47 One study demonstrated that homozygosity for the Arg389 mutation in ADRB1 was associated with a Obeticholic Acid mw 3-fold greater response in daytime diastolic pressure

following metoprolol administration.48 However, the association of ADRB1 mutations and blood pressure response to other beta-blockers has not been established. Genotype-driven variable response to beta-blockers may help to explain race-specific response to the drug class since the minor allele frequency for these polymorphisms is discrepant between African Americans and Caucasians.47 Inhibitors,research,lifescience,medical Other genes in beta-blocker response including ADRB2, G-protein beta3 subunit gene, and G-protein alpha unit gene have all been analyzed, but a consistent modulation of response to beta-blocker administration has not been demonstrated.47 The data with respect to beta-blocker therapy Inhibitors,research,lifescience,medical and the modulation of negative chronotropic effect by similar polymorphisms is somewhat underwhelming, where even the codon 389 ADRB1 polymorphism does not demonstrate consistent effect.49, 50 Since the late 1990s, beta-blockers have been central in the treatment of heart failure and have shown substantial benefits Inhibitors,research,lifescience,medical in mortality. Healthy subjects

who carry two copies of the variant allele Arg389Gly (rs1801253) in the beta-1 adrenergic receptor have greater chronotropic and blood pressure response following prescription of metoprolol. Consistent with this observation, patients with systolic dysfunction STK38 who carry two copies of this variant have greater improvements in ejection fraction after administration of metoprolol than noncarriers. While this has been also demonstrated with carvedilol, it is not the case with bucindolol. Cytochrome P450 2D6 is central in the metabolism of metoprolol and its polymorphisms have a profound influence on metoprolol pharmacokinetics. However, despite a genotype-based change in pharmacokinetic profile, changes in efficacy or the frequency of adverse effects have not been demonstrated. Thus far, there are certain aspects of beta-blocker pharmacogenetics that provide hope for the future.