The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort

Hoenig, M.; Walker, Philip J.; Gurnsey, Christine; Beadle, Karen; Johnson, Lambro A.

doi:10.1016/j.jacl.2011.01.001

Cited by 59 publications

(36 citation statements)

References 27 publications

(47 reference statements)

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“…All patients were of Croatian ancestry. Median (interquartile range) age was 56 (48-66) and 60 (53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) in the groups of patients with and without ADRs, respectively. The gender distribution was identical, and atorvastatin median prescribed dose was the same in both groups.…”

Section: Subjectsmentioning

confidence: 99%

“…We made every effort that controls came from the same source population as cases by asking those that reported ADRs to invite patients without ADRs to participate in the study. Furthermore, we did not consider other SNPs in genes such as ABCC2, ABCB1 and CYP3A5 but, according to available data, these SNPs could have only minor effect on ADRs caused by atorvastatin [5,65].…”

Section: Probability Of Adr (%)mentioning

confidence: 99%

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ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

et al. 2015

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Section: Subjectsmentioning

confidence: 99%

Section: Probability Of Adr (%)mentioning

confidence: 99%

ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

et al. 2015

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“…Hoenig et al [41] reported a significant association between the ABCB1 C3435T variant and atorvastatin-induced myalgia in 98 patients, but the clinical significance of this finding is limited because of the small number of events, the limited clinical discrimination, and the lack of replication. The ABCB1 3435T allele was more frequent in patients with atorvastatin-induced myalgia (80% vs 62%; p=0.043), but only 10 genotyped patients reported myalgia.…”

Section: Methodsmentioning

confidence: 99%

Pharmacogenetics of Statin-Induced Myopathy: A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants

Kitzmiller¹

2014

J Pharmacogenomics Pharmacoproteomics

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Statins are the most commonly prescribed drugs in the United States and are extremely effective in reducing major cardiovascular events in the millions of Americans with hyperlipidemia. However, many patients (up to 25%) cannot tolerate or discontinue statin therapy due to statin-induced myopathy (SIM). Patients will continue to experience SIM at unacceptably high rates or experience unnecessary cardiovascular events (as a result of discontinuing or decreasing their statin therapy) until strategies for predicting or mitigating SIM are identified. A promising strategy for predicting or mitigating SIM is pharmacogenetic testing, particularly of pharmacokinetic genetic variants as SIM is related to statin exposure. Data is emerging on the association between pharmacokinetic genetic variants and SIM. A current, critical evaluation of the literature on pharmacokinetic genetic variants and SIM for potential translation to clinical practice is lacking. This review focuses specifically on pharmacokinetic genetic variants and their association with SIM clinical outcomes. We also discuss future directions, specific to the research on pharmacokinetic genetic variants, which could speed the translation into clinical practice. For simvastatin, we did not find sufficient evidence to support the clinical translation of pharmacokinetic genetic variants other than SLCO1B1. However, SLCO1B1 may also be clinically relevant for pravastatin- and pitavastatin-induced myopathy, but additional studies assessing SIM clinical outcome are needed. CYP2D6*4 may be clinically relevant for atorvastatin-induced myopathy, but mechanistic studies are needed. Future research efforts need to incorporate statin-specific analyses, multi-variant analyses, and a standard definition of SIM. As the use of statins is extremely common and SIM continues to occur in a significant number of patients, future research investments in pharmacokinetic genetic variants have the potential to make a profound impact on public health.

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“…Hoenig et al [40] genotyped for C3435T 117 patients, treated with atorvastatin 80 mg for 6 weeks. Ten of those completing the study reported myalgia.…”

Section: Variants Of Abcb1mentioning

confidence: 99%

“…The T allele was more frequent and the C allele less frequent in patients with myalgia. The pharmacokinetics of most statins is altered by change in the activity of another efflux protein from the same family ABCG2, encoded by the ABCG2 gene [37,40] in particularly atorvastatin and rosuvastatin [38,41].…”

Section: Variants Of Abcb1mentioning

confidence: 99%

Statin Muscle Toxicity and Genetic Risk Factors

Mombelli¹

2013

Int J Genomic Med

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Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) can cause skeletal muscle toxicity; the risk of toxicity is elevated by drug interactions and pharmacogenetic factors that increase the concentration of statins in plasma.The genetic basis of statin-related muscle disorders is largely unknown. Statins are substrates for several membrane transporters that may mediate drug interactions. Potent inhibitors of cytochrome P450 (CYP450) especially CYP3A4, can significantly increase the plasma concentrations of the active forms of atorvastatin, lovastatin and simvastatin. Fluvastatin, which is metabolized by CYP2C9, is less prone to pharmacokinetic interactions, while pravastatin and rosuvastatin are not susceptible to any CYP inhibition. OATP1B1 can decrease the hepatic uptake of many statins, as well as the therapeutic index of these agents. Polymorphisms of CYP450 enzymes, SLCO1B1, ABCB1, and COQ2 gene, can induce statin intolerance. This review summarized the principal relations known between statin myotoxicity and genetic risk factors.

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The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort

Cited by 59 publications

References 27 publications

ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

Pharmacogenetics of Statin-Induced Myopathy: A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants

Statin Muscle Toxicity and Genetic Risk Factors

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