<i>CYP2C9</i>
            and
            <i>ABCG2</i>
            Polymorphisms as Risk Factors for Developing Adverse Drug Reactions in Renal Transplant Patients Taking Fluvastatin: A Case–Control Study

Skvrce, Nikica Mirošević; Božina, Nada; Zibar, Lada; Barišić, Ivan; Pejnović, Lana; Šarinić, Viola Macolić

doi:10.2217/pgs.13.135

Cited by 28 publications

(25 citation statements)

References 62 publications

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“…Single nucleotide polymorphism of ABCG2 421C>A (p.Q141K) results in its reduced activity – mRNA expression is maintained, but protein expression and function is reduced by 50–70% due to enhanced susceptibility to proteasomal degradation . Variant allele carriage is associated with a higher systemic exposure to several statins and sulfasalazine and with an increased incidence of adverse effects of statins and gefitinib . The present data suggest that it enhances the effect of valproate on exposure to lamotrigine.…”

Section: Discussionmentioning

confidence: 66%

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Domjanović

Lovrić

Trkulja

et al. 2018

Brit J Clinical Pharma

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Section: Discussionmentioning

confidence: 66%

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Domjanović

Lovrić

Trkulja

et al. 2018

Brit J Clinical Pharma

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“…Both CYP2C9*3 and *2 , as well as SLCO1B1 c.521T>C increase 3R,5S‐fluvastatin AUC. Of these, the CYP2C9*3 allele has previously been associated with fluvastatin‐induced adverse reactions . Moreover, the SLCO1B1 c.521T>C SNV increases simvastatin acid AUC more than threefold and associates with a markedly increased risk of simvastatin‐induced myotoxicity .…”

Section: Discussionmentioning

confidence: 99%

“…Of these, the CYP2C9*3 allele has previously been associated with fluvastatin-induced adverse reactions. 34 Moreover, the SLCO1B1 c.521T>C SNV increases simvastatin acid AUC more than threefold and associates with a markedly increased risk of simvastatin-induced myotoxicity. 20,35 As the effect of the c.521T>C SNV on 3R,5S-fluvastatin AUC is smaller than on simvastatin acid AUC, the increase in myotoxicity risk is also likely smaller.…”

Section: Discussionmentioning

confidence: 99%

Enantiospecific Pharmacogenomics of Fluvastatin

Hirvensalo

Tornio

Neuvonen

et al. 2019

Clin Pharma and Therapeutics

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The aim of this study was to investigate how variability in multiple genes related to pharmacokinetics affects fluvastatin exposure. We determined fluvastatin enantiomer pharmacokinetics and sequenced 379 pharmacokinetic genes in 200 healthy volunteers. CYP2C9*3 associated with significantly increased area under the plasma concentration‐time curve (AUC) of both 3R,5S‐fluvastatin and 3S,5R‐fluvastatin (by 67% and 94% per variant allele copy, P = 3.77 × 10−9 and P = 3.19 × 10−12). In contrast, SLCO1B1 c.521T>C associated with increased AUC of active 3R,5S‐fluvastatin only (by 34% per variant allele copy; P = 8.15 × 10−8). A candidate gene analysis suggested that CYP2C9*2 also affects the AUC of both fluvastatin enantiomers and that SLCO2B1 single‐nucleotide variations may affect the AUC of 3S,5R‐fluvastatin. Thus, SLCO transporters have enantiospecific effects on fluvastatin pharmacokinetics in humans. Genotyping of both CYP2C9 and SLCO1B1 may be useful in predicting fluvastatin efficacy and myotoxicity.

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“…However, with the exception of a study showing a genetic risk for fluvastatin-induced adverse effects, there are limited pharmacogenomic data available for statin response after kidney transplant. 50 …”

Section: Pharmacogenomics Of Statinsmentioning

confidence: 99%

Cardiovascular Pharmacogenomics—Implications for Patients With CKD

Cavallari

Mason

2016

Advances in Chronic Kidney Disease

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Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Thus, patients with CKD often require treatment with cardiovascular drugs, such as antiplatelet, antihypertensive, anticoagulant, and lipid-lowering agents. There is significant inter-patient variability in response to cardiovascular therapies, which contributes to risk for treatment failure or adverse drug effects. Pharmacogenomics offers the potential to optimize cardiovascular pharmacotherapy and improve outcomes in patients with cardiovascular disease, though data in patients with concomitant CKD are limited. The drugs with the most pharmacogenomic evidence are warfarin, clopidogrel, and statins. There are also accumulating data for genetic contributions to β-blocker response. Guidelines are now available to assist with applying pharmacogenetic test results to optimize warfarin dosing, selection of antiplatelet therapy after percutaneous coronary intervention, and prediction of risk for statin-induced myopathy. Clinical data, such as age, body size, and kidney function have long been used to optimize drug prescribing. An increasing number of institutions are also implementing genetic testing to be considered in the context of important clinical factors to further personalize drug therapy for patients with cardiovascular disease.

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CYP2C9 and ABCG2 Polymorphisms as Risk Factors for Developing Adverse Drug Reactions in Renal Transplant Patients Taking Fluvastatin: A Case–Control Study

Abstract: Our preliminary data demonstrate an association between fluvastatin-induced ADRs in RTRs and genetic variants in the CYP2C9 and ABCG2 genes.

Cited by 28 publications

References 62 publications

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Interaction betweenABCG2 421C>Apolymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy

Enantiospecific Pharmacogenomics of Fluvastatin

Cardiovascular Pharmacogenomics—Implications for Patients With CKD

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