ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis

Su, Jia; Xu, Hongyu; Yang, Jun; Yu, Qinglin; Yang, Shujun; Zhang, Jianjiang; Yao, Qi; Zhu, Yunyun; Luo, Yuan; Ji, Li; Zheng, Yibo; Yu, Jie

doi:10.1186/s12944-015-0114-2

Cited by 33 publications

(17 citation statements)

References 46 publications

(46 reference statements)

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“…A study on IMPROVE-IT reported a clear benefit in the reduction in major cardiovascular (CV) events with simvastatin and ezetimibe therapy[ 52 ]. The expression of the gene could also influence the lipid-lowering efficacy, and our most recent meta-analysis indicated that the ABCB1 C3435T polymorphism might be a pharmacogenomic biomarker for predicting clinical outcomes in patients with statins[ 53 ]. Therefore, we should consider the effect of statins in the present study, although we discovered that the ABCB1 C3435T polymorphism was related to the all-cause mortality under treatment with clopidogrel in CAD patients.…”

Section: Discussionmentioning

confidence: 99%

The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

Zhu

et al. 2017

PLoS ONE

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The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0.05). If patients did not have hypoproteinaemia or had hypertension, the SNP in rs1045642 was associated with CR (CC vs. TT: albumin ≥35, P = 0.042; hypertension, P = 0.045; C vs. T: albumin ≥35, P = 0.033; hypertension, P = 0.040). Additionally, the platelet inhibition of the CT+TT genotype in rs1128503 was larger than that of the CC genotype (P = 0.021). Multivariate logistic regression analysis showed that male, higher albumin and hsCRP decreased the risk of CR, and the stent size maybe positively correlated with CR. The SNP in rs1045642 was related to all-cause mortality (P = 0.024). We did not find any relationship between the methylation levels of the ABCB1 promoter and CR. In conclusions, our study indicated that ABCB1 polymorphisms might be useful in further evaluating the pathogenesis of CR.

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Section: Discussionmentioning

confidence: 99%

The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

Zhu

et al. 2017

PLoS ONE

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“…In particular, patients carrying the ABCB1 c.3435TT genotype showed a significant decrease in ABCB1 mRNA and protein levels [ 53 , 113 , 114 ]. A meta-analysis on hypercholesterolemic patients receiving statins examined the lipid-lowering efficacy and safety associated with the ABCB1 c.3435C>T. Results indicated that the comparison of CC + CT vs. TT was associated with a significant elevation in the serum HDL-C and total cholesterol levels upon statin treatment, and the ABCB1 c.3435CC vs. TT variants in homozygotes was correlated with decreases in LDL-C. No significant association was instead observed in serum triglycerides levels [ 54 ]. The c.3435C>T polymorphism in ABCB1 can also explain some heterogeneity of adverse response to statins.…”

Section: Pharmacogenetics Of Statinsmentioning

confidence: 99%

“…The c.3435T allele was more frequent in patients with atorvastatin-induced myalgia [ 21 , 55 ]. In addition, an ABCB1 c.3435C>T stratification analysis according to treatment duration found an association with a risk of myopathy in patients treated with statins for more than 5 months [ 54 ]. Currently, literature does report contrasting data on c.3435C>T SNP, whose association with the effect of statins on cholesterol and lipid levels is still debated.…”

Section: Pharmacogenetics Of Statinsmentioning

confidence: 99%

Pharmacogenetic Foundations of Therapeutic Efficacy and Adverse Events of Statins

Arrigoni

Fidilio

et al. 2017

IJMS

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Background: In the era of precision medicine, more attention is paid to the search for predictive markers of treatment efficacy and tolerability. Statins are one of the classes of drugs that could benefit from this approach because of their wide use and their incidence of adverse events. Methods: Literature from PubMed databases and bibliography from retrieved publications have been analyzed according to terms such as statins, pharmacogenetics, epigenetics, toxicity and drug–drug interaction, among others. The search was performed until 1 October 2016 for articles published in English language. Results: Several technical and methodological approaches have been adopted, including candidate gene and next generation sequencing (NGS) analyses, the latter being more robust and reliable. Among genes identified as possible predictive factors associated with statins toxicity, cytochrome P450 isoforms, transmembrane transporters and mitochondrial enzymes are the best characterized. Finally, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) transporter seems to be the best target for future studies. Moreover, drug–drug interactions need to be considered for the best approach to personalized treatment. Conclusions: Pharmacogenetics of statins includes several possible genes and their polymorphisms, but muscular toxicities seem better related to SLCO1B1 variant alleles. Their analysis in the general population of patients taking statins could improve treatment adherence and efficacy; however, the cost–efficacy ratio should be carefully evaluated.

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“…95 The organic anion-transporting polypeptide (OATP) 1B1 (gene name SLCOB1) arbitrates the hepatic uptake of all statins to a inconsistent level and the efflux transporters P-Glycoprotein / the breast cancer resistance protein (BCRP, gene name ABCG2) are engaged in the transport of most of the statin from the hepatocytes into bile. 96,97 Therefore drugs like cyclosporine, diltiazem that inhibit P-Glycoprotein may increase statin levels and precipitate toxicity. 98 With narrow therapeutic range drugs such as warfarin and digoxin statin increase anti coagulation effect, the reason expected to be that statin (simvastatin) inhibit metabolism of warfarin through CYP2C9.…”

Section: Drug Interactionsmentioning

confidence: 99%

Untitled

2016

IJPSR

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Statins, 3-hydroxymethyl-3-methylglutaryl coenzyme A reductase inhibitors, are considered safe in lowering hyperlipidemia and cardiovascular disease. Statin attempt to reduce cholesterol production in liver in dose dependent manner not only cause the muscle related problem but also leads to other untoward consequence like arthritis, diabetes, neurological disorders which arise as a result of scarcity in cholesterol production. Discontinuation or reduction in the dose of the statin usually leads to resolution of these side effects but the efficacy is questionable. Though the statin had come to market several decades ago, their harmful effects have been well understood very recently only after several randomized trials. The pleiotropic effects of statin have reported many benefits, but lack of randomized clinical trials make it limit to extend its indication beyond lipid lowering effects. There is still a controversy between their benefits and adverse effects of statin. The upcoming research should focus to resolve the above said confliction that could overcome its most adverse events-myopathy. If it so the statin with pleiotropic effect without any myopathic symptoms would be an excellent candidate among all other drugs. In this review, we discussed the myotoxicity, mechanism of myopathy, consequences as a result of statin"s attempt to reduce cholesterol production, risk factors for myopathy.

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ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis

Cited by 33 publications

References 46 publications

The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

Pharmacogenetic Foundations of Therapeutic Efficacy and Adverse Events of Statins

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