Impact of Apolipoprotein A5 Variants on Statin Treatment Efficacy

Hubacek, Jaroslav A.; Adámková, Věra; Prusíková, Martina; Šnejdrlová, Michaela; Hirschfeldova, Katerina; Lánská, Věra; Češka, R.; Vrablík, M.

doi:10.2217/pgs.09.17

Cited by 34 publications

(31 citation statements)

References 22 publications

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“…The polymorphism of ApoA5 has been demonstrated to be tightly associated with ischemic stroke and hyperlipidemia [25]. Our data showed here that the SNP rs662799 affects the effectiveness of atorvastatin in all patients and in both Han and Uighur populations, which is in accordance with previous report in Caucasians population [26]. Thus the polymorphisms of APOA5 affect the effectiveness of atorvastatin.…”

Section: Discussionsupporting

confidence: 93%

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Yue

Bai

Zhang

et al. 2016

Cell Physiol Biochem

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Background/Aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔLDL and ΔLDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔTG (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of ΔHDL (p < 0.05); the SNP rs662799 significantly affected the ratio of ΔLDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

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Section: Discussionsupporting

confidence: 93%

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Yue

Bai

Zhang

et al. 2016

Cell Physiol Biochem

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“…11,19,20 The same region was also shown in large genome-wide association studies to be associated with baseline triglyceride and HDL-C levels. One limitation of our study—inherent in the sample set—is that previous use of other drug groups (statins, fibrates, niacin) prior to initiating the drug under investigation was not accounted for in the analyses.…”

Section: Discussionmentioning

confidence: 64%

“…8 We have previously shown that SNPs in the BUD13-APOA5 region affect HDL-C response to fibrate-statin combination therapy. 9,10 A recent study by Hubacek et al 11 showed that SNPs within the APOA5 gene region had an effect on LDL-C response to statins. In this study, we examined the association between common genetic variants in the APOA5-BUD13 gene region and change in LDL-C, HDL-C, and TG levels in response to statin therapy in the context of a longitudinal population study.…”

Section: Introductionmentioning

confidence: 99%

Differential Lipid Response to Statins Is Associated With Variants in the BUD13–APOA5 Gene Region

O'Brien

Schrodi

et al. 2015

Journal of Cardiovascular Pharmacology

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Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single-nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for three SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P=1.59E-04) while the minor allele at rs12806755 was associated with a similar response to lovastatin (P=1.92E-04). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P=6.68E-04) with some patients with the minor allele having LDL-C increase following therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population.

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“…Besides, drugs such as pravastatin and rotuvastatin are not susceptible to CYP inhibition, but are substrates of the a hepatic transporter and solute organic anion-transporting polypeptide (OATP) 1B1 (encoded by the SLCO1B1 gene) which is responsible for liver transportation of the statins 154 . Variants of the apolipoprotein, particularly the apo E and apo A5 also have their share in these processes [155][156][157][158] . Similarly, genetically impaired ABCG2 transporter efflux activity results in a marked increase in systemic exposure to various statins 159 .…”

Section: Genetics and Drug Therapy Of Coronary Artery Diseasementioning

confidence: 99%

Gene Polymorphism and Coronary Heart Disease

Dzimiri¹

2012

Coronary Artery Disease - New Insights and Novel Approaches

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Impact of Apolipoprotein A5 Variants on Statin Treatment Efficacy

Abstract: Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.

Cited by 34 publications

References 22 publications

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients

Differential Lipid Response to Statins Is Associated With Variants in the BUD13–APOA5 Gene Region

Gene Polymorphism and Coronary Heart Disease

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