We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Associations between SLCO1B1, APOE and CYP2C9 and lipid-lowering efficacy and pharmacokinetics of fluvastatin: a meta-analysis

    Zi Hao Zhang

    Beijing Shijitan Hospital Affiliated to Capital Medical University, No. 10, Tie Medical Road, Haidian District, Beijing, China

    ,
    Li Chao Yue Sun

    Beijing Shijitan Hospital Affiliated to Capital Medical University, No. 10, Tie Medical Road, Haidian District, Beijing, China

    ,
    Hong Yan Gu

    Beijing Shijitan Hospital Affiliated to Capital Medical University, No. 10, Tie Medical Road, Haidian District, Beijing, China

    ,
    De Chun Jiang

    *Author for correspondence:

    E-mail Address: jiangdechun@sina.com

    Beijing Shijitan Hospital Affiliated to Capital Medical University, No. 10, Tie Medical Road, Haidian District, Beijing, China

    &
    Zhan Miao Yi

    **Author for correspondence:

    E-mail Address: yzm@bjmu.edu.cn

    Peking University Third Hospital, No. 49, North Huayuan Road, Haidian District, Beijing, China

    Published Online:https://doi.org/10.2217/pgs-2023-0004

    Objective: This meta-analysis was designed to investigate the associations between SLCO1B1, APOE and CYP2C9 and the lipid-lowering effects and pharmacokinetics of fluvastatin. Methods: Studies were searched from inception to March 2023, including three SNPs related to fluvastatin, SLCO1B1, CYP2C9 and APOE. Weighted mean differences and corresponding 95% CIs were analyzed to evaluate the associations between SNPs and outcomes. Results:SLCO1B1 521T>C was associated with lower total cholesterol and low-density lipoprotein reduction. Patients carrying 521CC or total cholesterol had a significantly higher area under the curve than those carrying 521TT, but no significant difference existed. Conclusion:CYP2C9 and SLCO1B1 may be associated with the efficacy and pharmacokinetics of fluvastatin.

    References

    • 1. China Cardiovascular Health and Disease Report Writing Group. Summary of the China Cardiovascular Health and Disease Report 2020. Chin. Circ. J. 36(06), 521–545 (2021).
    • 2. Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis 290, 140–205 (2019).
    • 3. Baigent C, Keech A, Kearney PM. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366(9493), 1267–1278 (2005).
    • 4. Junren Z, Runlin G, Shuiping Z. Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China (2016 Revised Edition). Chin. Circ. J. 31(10), 937–953 (2016).
    • 5. Donnelly LA, Palmer CN, Whitley AL. Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study. Pharmacogenet. Genomics 18(4), 279–287 (2008).
    • 6. Pasanen MK, Miettinen TA, Gylling H. Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate. Pharmacogenet. Genomics 18(10), 921–926 (2008).
    • 7. Hu L, Shuiping Z. Apolipoprotein E and cholesteryl ester transporter protein gene polymorphisms in relation to coronary heart disease. Clin. Focus 24(24), 2127–2130 (2009).
    • 8. Saxena R, Voight BF, Lyssenko V. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316(5829), 1331–1336 (2007).
    • 9. Utermann G. Apolipoprotein E polymorphism in health and disease. Am. Heart J. 113(2 Pt 2), 433–440 (1987).
    • 10. Link E, Parish S, Armitage J. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N. Engl. J. Med. 359(8), 789–799 (2008).
    • 11. Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin. Pharmacol. Ther. 80(4), 356–366 (2006).
    • 12. Niemi M. Role of OATP transporters in the disposition of drugs. Pharmacogenomics 8(7), 787–802 (2007).
    • 13. Meyer ZSH, Albers M, Baumeister SE. Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort. Pharmacogenet. Genomics 25(1), 8–18 (2015).
    • 14. Couvert P, Giral P, Dejager S. Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy. Pharmacogenomics 9(9), 1217–1227 (2008).
    • 15. Tong Y. Advances in the pharmacogenomics of fluvastatin. Drug Eval. 17(21), 3–5 (2020).
    • 16. Xiang Q, Wu W, Zhao N. The influence of genetic polymorphisms in drug metabolism enzymes and transporters on the pharmacokinetics of different fluvastatin formulations. Asian J. Pharm. Sci. 15(2), 264–272 (2020).
    • 17. Zhou Q, Ruan ZR, Yuan H. CYP2C9*3(1075A>C), MDR1 G2677T/A and MDR1 C3435T are determinants of inter-subject variability in fluvastatin pharmacokinetics in healthy Chinese volunteers. Arzneimittelforschung 62(11), 519–524 (2012).
    • 18. Moher D, Liberati A, Tetzlaff J. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med. 151(4), 264–269 (2009).
    • 19. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21(11), 1539–1558 (2002).
    • 20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control. Clin. Trials 7(3), 177–188 (1986).
    • 21. Zuccaro P, Mombelli G, Calabresi L. Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacol. Res. 55(4), 310–317 (2007).
    • 22. Kirchheiner J, Kudlicz D, Meisel C. Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin. Pharmacol. Ther. 74(2), 186–194 (2003).
    • 23. Ballantyne CM, Herd JA, Stein EA. Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy. J. Am. Coll. Cardiol. 36(5), 1572–1578 (2000).
    • 24. Weining L, Yong X, Anping X. Association of apolipoprotein E gene polymorphisms with lipid-lowering efficacy of fluvastatin. Lab. Med. Clin. 8(18), 2181–2182 (2011).
    • 25. Dergunov AD, Perova NV, Visvikis S. Time-dependent lipid response on fluvastatin therapy of patients with hypercholesterolemia sensitive to apoE phenotype. Vascul. Pharmacol. 40(5), 237–245 (2003).
    • 26. Buzková H, Pechandová K, Danzig V. Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population. Med. Sci. Monit. 18(8), R512–R517 (2012).
    • 27. Li ZQ, Li CY, Wan X. Effect of CYP2C9*3 gene polymorphism on lipid-lowering efficacy of fluvastatin in a Chinese hyperlipidemic population. Trop. J. Pharm. Res. 16(9), 2261–2265 (2017).
    • 28. Cooper-DeHoff RM, Niemi M, Ramsey LB. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin. Pharmacol. Ther. 111(5), 1007–1021 (2022).