Influence of APOA5 Locus on the Treatment Efficacy of Three Statins: Evidence From a Randomized Pilot Study in Chinese Subjects

Hua, Sha; Zhang, Jun; Li, Jing; Wu, Weiwei; Xu, Ning; Luo, Guanghua; Zhao, Jing

doi:10.3389/fphar.2018.00352

Cited by 12 publications

(7 citation statements)

References 55 publications

(71 reference statements)

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“…The frequency of the APOA5 −1131C allele is higher in East Asians (>25%) than in Westerners (9%‐16%) . APOA5 −1131 T>C was also proved to be associated with the statins (simvastatin, atorvastatin or rosuvastatin) efficacy on the reduction of LDL‐C levels . 56 C>G was identified as a signal peptide functional mutant, which led to increased plasma TG and low HDL levels .…”

Section: Resultsmentioning

confidence: 99%

Pharmacogenetics of statins treatment: Efficacy and safety

Guan

et al. 2019

J Clin Pharm Ther

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What is known and objective: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke.However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. Methods:We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins.We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. Results and discussion:The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. What is new and conclusion:In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele. K E Y W O R D S cytochrome P450, gene polymorphism, pharmacogenetics, statins, transporter | 859 GUAN et Al.

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Section: Resultsmentioning

confidence: 99%

Pharmacogenetics of statins treatment: Efficacy and safety

Guan

et al. 2019

J Clin Pharm Ther

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“…This SNP was also associated with dyslipidemia [ 34 ] and circulating triglycerides [ 35 ]. Additional APOA5 SNPs are associated with lipid levels [ 35 ], metabolic syndrome [ 36 ] and statin treatment efficacy [ 37 ]. The Cerebellin 1 Precursor ( CBLN1 ) rs1420601 SNP is associated with whole-body fat-free mass and isoleucine levels (UK Biobank), as well as with impaired BCAA metabolism and T2D risk [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Genetically Predicted BCAA Levels with Muscle Fiber Size in Athletes Consuming Protein

Hall

Semenova

Бондарева

et al. 2022

Genes

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Branched-chain amino acid (BCAA) levels are associated with skeletal muscle cross-sectional area (CSA). Serum BCAA levels are enhanced by whey protein supplementation (WPS), and evidence in clinical populations suggests an association of single nucleotide polymorphisms (SNPs) with BCAA metabolite levels. It is not known whether the same SNPs are associated with the ability to catabolise BCAAs from exogenous sources, such as WPS. The present study investigated whether possessing a higher number of alleles associated with increased BCAA metabolites correlates with muscle fiber CSA of m. vastus lateralis in physically active participants, and whether any relationship is enhanced by WPS. Endurance-trained participants (n = 75) were grouped by self-reported habitual WPS consumption and genotyped for five SNPs (PPM1K rs1440580, APOA5 rs2072560, CBLN1 rs1420601, DDX19B rs12325419, and TRMT61A rs58101275). Body mass, BMI, and fat percentage were significantly lower and muscle mass higher in the WPS group compared to Non-WPS. The number of BCAA-increasing alleles was correlated with fiber CSA in the WPS group (r = 0.75, p < 0.0001) and was stronger for fast-twitch fibers (p = 0.001) than slow-twitch fibers (p = 0.048). Similar results remained when corrected for multiple covariates (age, physical activity, and meat and dairy intake). No correlation was found in the Non-WPS group. This study presents novel evidence of a positive relationship between BCAA-increasing alleles and muscle fiber CSA in athletes habitually consuming WPS. We suggest that a high number of BCAA-increasing alleles improves the efficiency of WPS by stimulation of muscle protein synthesis, and contributes to greater fiber CSA.

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“…The recommended dose of ATV is between 10 and 80 mg once per day, and the preferred dose among Chinese is 20 mg (Hua et al. 2018 ; Yang et al. 2018 ).…”

Section: Discussionmentioning

confidence: 99%

QiShenYiQi pills, a Chinese patent medicine, increase bioavailability of atorvastatin by inhibiting Mrp2 expression in rats

Ding

Xiao

Meng

et al. 2022

Pharmaceutical Biology

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Context Atorvastatin (ATV) and QiShenYiQi pills (QSYQ), a Chinese patent medicine, are often co-prescribed to Chinese cardiovascular patients. The effects of QSYQ on the pharmacokinetics of ATV have not been studied. Objective We investigated the influence of QSYQ on the pharmacokinetics of ATV and its metabolites upon oral or intravenous administration of ATV to rats. Materials and methods Sprague-Dawley rats ( n = 5/group) were pre-treated with oral QSYQ (675 mg/kg) or vehicle control for 7 days and then orally administrated ATV (10 mg/kg) or intravenously administrated ATV (2 mg/kg). Serum concentrations of ATV and metabolites were determined by ultra-high performance liquid chromatography tandem mass spectrometry. Expression of metabolic enzymes and transporters in jejunum and ileum were measured by quantitative real-time PCR and Western blot. Results QSYQ resulted in an increase of AUC 0-12 h of ATV from 226.67 ± 42.11 to 408.70 ± 161.75 ng/mL/h and of C max of ATV from 101.46 ± 26.18 to 198.00 ± 51.69 ng/mL and in an increased of para- hydroxy atorvastatin from 9.07 ± 6.20 to 23.10 ± 8.70 ng/mL in rats administered ATV orally. No change was observed in rats treated intravenously. The expression of multidrug resistance-associated protein 2 mRNA and protein decreased in ileum, and the mRNA of P-glycoprotein decreased in jejunum, though no change in protein expression was found. Discussion and conclusions QSYQ increased bioavailability of ATV administered orally through inhibiting the expression of Mrp2 in ileum. Clinicians should pay close attention to potential drug-drug interactions between ATV and QSYQ.

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Influence of APOA5 Locus on the Treatment Efficacy of Three Statins: Evidence From a Randomized Pilot Study in Chinese Subjects

Cited by 12 publications

References 55 publications

Pharmacogenetics of statins treatment: Efficacy and safety

Pharmacogenetics of statins treatment: Efficacy and safety

Association of Genetically Predicted BCAA Levels with Muscle Fiber Size in Athletes Consuming Protein

QiShenYiQi pills, a Chinese patent medicine, increase bioavailability of atorvastatin by inhibiting Mrp2 expression in rats

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