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Efficacy and safety of statins in ethnic differences: a lesson for application in Indigenous Australian patient care

    Lemlem G Gebremichael

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    ,
    Vijayaprakash Suppiah

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    Australian Centre for Precision Health, University of South Australia, Adelaide, SA 5000, Australia

    ,
    Michael D Wiese

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    ,
    Lorraine Mackenzie

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    ,
    Craig Phillips

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    ,
    Desmond B Williams

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    &
    Michael S Roberts

    *Author for correspondence: Tel.: +61 883 022 815;

    E-mail Address: Michael.Roberts@unisa.edu.au

    UniSA Clinical & Health Science, University of South Australia, Adelaide, SA 5000, Australia

    Therapeutics Research Centre, Diamantina Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia

    Basil Hetzel Institute for Translational Medical Research, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville, SA 5011, Australia

    Published Online:https://doi.org/10.2217/pgs-2020-0152

    Although statins are effective in treating high cholesterol, adverse effects do occur with their use. Efficacy and tolerability vary among statins in different ethnic groups. Indigenous Australians have a high risk for cardiovascular and kidney diseases. Prescribing statins to Indigenous Australians with multi-morbidity requires different strategies to increase efficacy and reduce their toxicity. Previous studies have reported that Indigenous Australians are more susceptible to severe statin-induced myopathies. However, there is a lack of evidence in the underlying genetic factors in this population. This review aims to identify: inter-ethnic differences in the efficacy and safety of statins; major contributing factors accounting for any identified differences; and provide an overview of statin-induced adverse effects in Indigenous Australians.

    References

    • 1. Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug–drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol. Ther. 112(1), 71–105 (2006).
    • 2. Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J. Am. Coll. Cardiol. 61(25), 2495–2502 (2013).
    • 3. Ieiri S, Higuchi I, Sugiyama Y. Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs. Expert Opin. Drug Metab. Toxicol. 5(7), 703–729 (2009).
    • 4. Wang EJ, Casciano CN, Clement RP, Johnson WW. HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm. Res. 18(6), 800–806 (2001).
    • 5. Ho RH, Tirona RG, Leake BF et al. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130(6), 1793–1806 (2006).
    • 6. Schachter Michael. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol. 19(1), 117–125 (2005).
    • 7. Ballantyne CM. Section III therapy. Clinical lipidology: a companion to Braunwald’s heart disease. Elsevier 254 (2014).
    • 8. World Health Organization (WHO). Cardiovascular diseases (CVDs) 2017. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
    • 9. Australian Government Department of Health. Cardiovascular disease 2016. http://www.health.gov.au/
    • 10. Australian Health Minister’s Advisory Council.Aboriginal and Torres Strait Islander Health Performance Framework 2012 Report (2012). https://www1.health.gov.au/internet/main/Publishing.nsf/Content/F766FC3D8A697685CA257BF0001C96E8/$File/hpf-2012.pdf
    • 11. Australian Bureau of Statistics (ABS). Australia's leading causes of death, 2018 (2019). https://www.abs.gov.au/statistics/health/causes-death/causes-death-australia/2018
    • 12. Graham I, Atar D, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur. Heart J. 28(19), 2375–2414 (2007).
    • 13. Taylor F, Huffman MD, Macedo AF et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst.Rev. 31(1), CD004816 (2013).
    • 14. Stancu C, Sima A. Statins: mechanism of action and effects. J. Cell. Mol. Med. 5(4), 378–387 (2001).
    • 15. Ofori-Asenso R, Ilomaki J, Zomer E, Curtis AJ, Zoungas S, Liew D. A 10-year trend in statin use among older adults in Australia: an analysis using National Pharmacy Claims Data. Cardiovasc. Drugs Ther. 32(3), 265–272 (2018).
    • 16. Gupta M, Braga MFB, Teoh H, Tsigoulis M, Verma S. Statin effects on LDL and HDL cholesterol in South Asian and white populations. J. Clin. Pharmacol. 49(7), 831–837 (2009).
    • 17. Hippisley-Cox Julia, Coupland Carol. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 340, c2197 (2010).
    • 18. Gu Q, Paulose-Ram R, Burt VL, BK K. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012. In: NCHS Data Brief. No. 177. National Center for Health Statistics, MD, USA (2014).
    • 19. Scripture CD, Pieper JA. Clinical pharmacokinetics of fluvastatin. Clin. Pharmacokinet. 40(4), 263–281 (2001).
    • 20. Gazzerro P, Proto MC, Gangemi G et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol. Rev. 64(1), 102 (2012).
    • 21. Fischer V, Johanson L, Heitz F et al. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab. Dispos. 27(3), 410–416 (1999).
    • 22. Yang D-J, Hwang LS. Study on the conversion of three natural statins from lactone forms to their corresponding hydroxy acid forms and their determination in Pu-Erh tea. J. Chromatogr. A 1119(1), 277–284 (2006).
    • 23. Kellick KA, Bottorff M, Toth PP. A clinician’s guide to statin drug–drug interactions. J. Clin. Lipidol. 8(3), S30–S46 (2014).
    • 24. Hsiang B, Zhu Y, Wang Z et al. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J. Biol. Chem. 274(52), 37161–37168 (1999).
    • 25. Haffner SM, D'Agostino Jr R, Goff D et al. LDL size in African–Americans, Hispanics, and Non-Hispanic whites. Arterioscler. Thromb. Vasc. Biol. 19(9), 2234–2240 (1999).
    • 26. Haffner SM, Mykkänen L, Valdez RA, Paidi M, Stern MP, Howard BV. LDL size and subclass pattern in a biethnic population. Arteriosclerosis and thrombosis. J. Vasc. Biol. 13(11), 1623–1630 (1993).
    • 27. Kulkarni KR, Markovitz JH, Nanda NC, Segrest JP. Increased prevalence of smaller and denser LDL particles in Asian Indians. Arterioscler. Thromb. Vasc. Biol. 19, 2749–2755 (1999).
    • 28. Cho HK, Shin G, Ryu SK, Jang Y, Day SP, Stewart G et al. Regulation of small dense LDL concentration in Korean and Scottish men and women. Atherosclerosis 164(1), 187–193 (2002).
    • 29. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260(13), 1917–1921 (1988).
    • 30. Ivanova EA, Myasoedova VA, Melnichenko AA, Grechko AV, Orekhov AN. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxid. Med. Cell. Longevity. 2017, 10 (2017).
    • 31. Orekhov AN, Tertov VV, Mukhin DN. Desialylated low density lipoprotein--naturally occurring modified lipoprotein with atherogenic potency. Atherosclerosis 86(2–3), 153–161 (1991).
    • 32. Thongtang N, Diffenderfer MR, Ooi EMM et al. Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin. J. Lipid Res. 58(7), 1315–1324 (2017).
    • 33. Hua J, Malinski T. Variable effects of LDL subclasses of cholesterol on endothelial nitric oxide/peroxynitrite balance: the risks and clinical implications for cardiovascular disease. Int. J. Nanomedicine 14, 8973–8987 (2019).
    • 34. Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation 106(15), 1930–1937 (2002).
    • 35. Berneis K, Jeanneret C, Muser J, Felix B, Miserez AR. Low-density lipoprotein size and subclasses are markers of clinically apparent and non-apparent atherosclerosis in Type 2 diabetes. Metabolism 54(2), 227–234 (2005).
    • 36. Fan J, Liu Y, Yin S et al. Small dense LDL cholesterol is associated with metabolic syndrome traits independently of obesity and inflammation. Nutr. Metab. (Lond.) 16, 7 (2019).
    • 37. Griffin BA, Caslake MJ, Yip B, Tait GW, Packard CJ, Shepherd J. Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation. Atherosclerosis 83(1), 59–67 (1990).
    • 38. Packard CJ. Evolution of the HMG CoA reductase inhibitors (statins) in cardiovascular medicine. Br. J. Cardiol. 11(2), 129–136 (2004).
    • 39. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am. J. Cardiol. 105(1), 69–76 (2010).
    • 40. Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* trial). Am. J. Cardiol. 92(2), 152–160 (2003).
    • 41. Shuhaili MFRMA, Samsudin IN, Stanslas J, Hasan S, Thambiah SC. Effects of different types of statins on lipid profile: a perspective on Asians. Int. J. Endocrinol. Metab. 15(2), e43319 (2017).
    • 42. Oni-Orisan A, Hoffmann TJ, Ranatunga D et al. Characterization of statin low-density lipoprotein cholesterol dose-response using electronic health records in a large population-based cohort. Circ. Genomic Precis. Med. 11(9), e002043 (2018).
    • 43. Yood MU, McCarthy BD, Kempf J et al. Racial differences in reaching target low-density lipoprotein goal among individuals treated with prescription statin therapy. Am. Heart J. 152(4), 777–784 (2006).
    • 44. Clark LT, Maki KC, Galant R, Maron DJ, Pearson TA, Davidson MH. Ethnic differences in achievement of cholesterol treatment goals: results from the National Cholesterol Education Program Evaluation Project Utilizing Novel E-Technology II. J. Gen. Intern. Med. 21(4), 320–326 (2006).
    • 45. Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton Jr VP, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 291, 2821–2827 (2004).
    • 46. Kouji K, Noboru T, Margaret BE, Ernst SJ. Pharmacogenetics of HMG-CoA reductase inhibitors: exploring the potential for genotype-based individualization of coronary heart disease management. Atherosclerosis 177(2), 219–234 (2004).
    • 47. Zhu JR, Tomlinson B, Ro YM, Sim KH, Lee YT, Sriratanasathavorn C. A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study). Curr. Med. Res. Opin. 23(12), 3055–3068 (2007).
    • 48. Deedwania PC, Gupta M, Stein M, Ycas J, Gold A. Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of coronary heart disease (from the IRIS trial). Am. J. Cardiol. 99(11), 1538–1543 (2007).
    • 49. Ferdinand KC, Clark LT, Watson KE et al. Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial. Am. J. Cardiol. 97(2), 229–235 (2006).
    • 50. Ramon L, Yčas J, Michael S, Haffner S. STARSHIP Study Group Comparison of rosuvastatin versus atorvastatin in Hispanic-Americans with hypercholesterolemia (from the STARSHIP trial). Am. J. Cardiol. 98(6), 768–773 (2006).
    • 51. Chapman N, Chang CL, Caulfield M et al. Ethnic variations in lipid-lowering in response to a statin (EVIREST): a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Ethn. Dis. 21(2), 150–157 (2011).
    • 52. Gandelman K, Fung GL, Messig M, Laskey R. Systemic exposure to atorvastatin between Asian and Caucasian subjects: a combined analysis of 22 studies. Am. J. Ther. 19(3), 164–173 (2012).
    • 53. Naito R, Miyauchi K, Daida H. Racial differences in the cholesterol-lowering effect of statin. J. Atheroscler. Thromb. 24(1), 19–25 (2017).
    • 54. Nakamura H, Arakawa K, Itakura H et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA study): a prospective randomised controlled trial. Lancet 368(9542), 1155–1163 (2006).
    • 55. Li YF, Feng QZ, Gao WQ, Zhang XJ, Huang Y, Chen YD. The difference between Asian and Western in the effect of LDL-C lowering therapy on coronary atherosclerotic plaque: a meta-analysis report. BMC Cardiovasc. Disord. 15, 6 (2015).
    • 56. Lee E, Ryan S, Birmingham B et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin. Pharmacol. Ther. 78(4), 330–341 (2005).
    • 57. Tomita Y, Maeda K, Sugiyama Y. Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism. Clin. Pharmacol. Ther. 94(1), 37–51 (2013).
    • 58. Warrington S, Nagakawa S, Hounslow N. Comparison of the pharmacokinetics of pitavastatin by formulation and ethnic group: an openlabel, single-dose, two-way crossover pharmacokinetic study in healthy Caucasian and Japanese men. Clin. Drug Investig. 31, 735–743 (2011).
    • 59. Ho RH, Choi L, Lee W et al. Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants. Pharmacogenet. Genomics 17(8), 647–56 (2007).
    • 60. Birmingham BK, Bujac SR, Elsby R et al. Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States. Eur. J. Clin. Pharmacol. 71(3), 329–340 (2015).
    • 61. Bahadir MA, Oguz A, Uzunlulu M, Bahadir O. Effects of different statin treatments on small dense low-density lipoprotein in patients with metabolic syndrome. J. Atheroscler. Thromb. 16(5), 684–690 (2009).
    • 62. Nishikido T, Oyama J-I, Keida T, Ohira H, Node K. High-dose statin therapy with rosuvastatin reduces small dense LDL and MDA-LDL: the Standard versus high-dose therApy with Rosuvastatin for lipiD lowering (SARD) trial. J. Cardiol. 67(4), 340–346 (2016).
    • 63. Clementia A, Kim JC, Florisa M et al. Statin therapy is associated with decreased small, dense low-density lipoprotein levels in patients undergoing peritoneal dialysis. Contrib. Nephrol. 178, 111–115 (2012).
    • 64. Choi CU, Seo HS, Lee EM et al. Statins do not decrease small, dense low-density lipoprotein. Tex. Heart Inst. J. 37(4), 421–428 (2010).
    • 65. O'Neal DN, Piers LS, Iser DM et al. Australian Aboriginal people and Torres Strait Islanders have an atherogenic lipid profile that is characterised by low HDL-cholesterol level and small LDL particles. Atherosclerosis 201(2), 368–377 (2008).
    • 66. Crestor®, package insert. AstraZeneca Pharmaceuticals, DE, USA.
    • 67. Hua WJ, Hua WX, Fang HJ. The role of OATP1B1 and BCRP in pharmacokinetics and DDI of novel statins. Cardiovasc. Ther. 30(5), e234–e241 (2012).
    • 68. Urquhart BL, Tirona RG, Kim RB. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J. Clin. Pharmacol. 47(5), 566–578 (2007).
    • 69. Krauss RM, Mangravite LM, Smith JD et al. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme A reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation 117(12), 1537–1544 (2008).
    • 70. Medina MW, Gao F, Ruan W, Rotter JI, Krauss RM. Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin. Circulation 118(4), 355–362 (2008).
    • 71. Chung JY, Cho SK, Oh ES et al. Effect of HMGCR variant alleles on low-density lipoprotein cholesterol: lowering response to atorvastatin in healthy Korean subjects. J. Clin. Pharmacol. 52(3), 339–346 (2012).
    • 72. Hiura Y, Tabara Y, Kokubo Y et al. Association of the functional variant in the 3-hydroxy-3-methylglutaryl-coenzyme a reductase gene with low-density lipoprotein-cholesterol in Japanese. Circ. J. 74(3), 518–522 (2010).
    • 73. Krauss RM, Mangravite LM, Smith JD et al. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation 117(12), 1537–1544 (2008).
    • 74. Williams JA, Ring BJ, Cantrell VE et al. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab. Dispos. 30(8), 883–891 (2002).
    • 75. Park JE, Kim KB, Bae SK, Moon BS, Liu KH, Shin JG. Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin. Xenobiotica 38(9), 1240–1251 (2008).
    • 76. Zhou Y, Ingelman-Sundberg M, Lauschke VM. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin. Pharmacol. Ther. 102(4), 688–700 (2017).
    • 77. Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 11(4), 274–286 (2011).
    • 78. Okubo M, Murayama N, Shimizu M, Shimada T, Guengerich FP, Yamazaki H. The CYP3A4 intron 6 C >T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes. J. Toxicol. Sci. 38(3), 349–354 (2013).
    • 79. Elens L, Becker ML, Haufroid V et al. Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study. Pharmacogenet. Genomics 21(12), 861–866 (2011).
    • 80. Kim KA, Park PW, Lee OJ, Kang DK, Park JY. Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J. Clin. Pharmacol. 47(1), 87–93 (2007).
    • 81. Kivisto KT, Niemi M, Schaeffeler E et al. Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics 14(8), 523–525 (2004).
    • 82. Rosdi RA, Mohd Yusoff N, Ismail R et al. High allele frequency of CYP2C9*3 (rs1057910) in a Negrito’s subtribe population in Malaysia; Aboriginal people of Jahai. Ann. Hum. Biol. 43(5), 445–450 (2016).
    • 83. Li Z-q, Li C-y, Wan X, Wang F. 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).
    • 84. Skvrce NM, Bozina N, Zibar L, Barisic I, Pejnovic L, Sarinic VM. CYP2C9 and ABCG2 polymorphisms as risk factors for developing adverse drug reactions in renal transplant patients taking fluvastatin: a case–control study. Pharmacogenomics 14(12), 1419–1431 (2013).
    • 85. Tirona RG, Leake BF, Merino G, Kim RB. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J. Biol. Chem. 276(38), 35669–35675 (2001).
    • 86. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmacogenomics Pers. Med. 9, 97–106 (2016).
    • 87. Tachibana-Iimori R, Tabara Y, Kusuhara H et al. Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors. Drug Metab. Pharmacokinet. 19(5), 375–380 (2004).
    • 88. Oshiro C, Mangravite L, Klein T, Altman R. PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenet. Genomics. 20(3), 211–216 (2010).
    • 89. Kim SR, Saito Y, Sai K et al. Genetic variations and frequencies of major haplotypes in SLCO1B1 encoding the transporter OATP1B1 in Japanese subjects: SLCO1B1*17 is more prevalent than *15. Drug Metab. Pharmacokinet. 22(6), 456–461 (2007).
    • 90. Mwinyi J, Köpke K, Schaefer M, Roots I, Gerloff T. Comparison of SLCO1B1 sequence variability among German, Turkish, and African populations. Eur. J. Clin. Pharmacol. 64(3), 257–266 (2008).
    • 91. Marja Pasanen. Pharmacogenetics of SLCO1B1: population genetics and effect on statins [PhD thesis]. University of Helsinki, Finland (2008).
    • 92. Jada SR, Xiaochen S, Yan LY et al. Pharmacogenetics of SLCO1B1: haplotypes, htSNPs and hepatic expression in three distinct Asian populations. Eur. J. Clin. Pharmacol. 63(6), 555–563 (2007).
    • 93. Chang C, Pang KS, Swaan PW, Ekins S. Comparative pharmacophore modeling of organic anion transporting polypeptides: a meta-analysis of rat Oatp1a1 and human OATP1B1. J. Pharmacol. Exp. Ther. 314(2), 533–541 (2005).
    • 94. Nozawa T, Nakajima M, Tamai I et al. Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. J. Pharmacol. Exp. Ther. 302(2), 804–813 (2002).
    • 95. Niemi M. Transporter pharmacogenetics and statin toxicity. Clin. Pharmacol. Ther. 87(1), 130–133 (2010).
    • 96. Deng JW, Song IS, Shin HJ et al. The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet. Genomics 18(5), 424–433 (2008).
    • 97. Chung JY, Cho JY, Yu KS et al. Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers. Clin. Pharmacol. Ther. 78(4), 342–350 (2005).
    • 98. Ieiri I, Suwannakul S, Maeda K et al. SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers. Clin. Pharmacol. Ther. 82(5), 541–547 (2007).
    • 99. Nishizato Y, Ieiri I, Suzuki H et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clin. Pharmacol. Ther. 73(6), 554–565 (2003).
    • 100. Niemi M, Schaeffeler E, Lang T et al. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 14(7), 429–440 (2004).
    • 101. Choi JH, Lee MG, Cho JY, Lee JE, Kim KH, Park K. Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans. Clin. Pharmacol. Ther. 83(2), 251–257 (2008).
    • 102. Group TSC. SLCO1B1 variants and statin-induced myopathy: a genomewide study. N. Engl. J. Med. 359(8), 789–799 (2008).
    • 103. Brunham LR, Lansberg PJ, Zhang L et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J. 12(3), 233–237 (2012).
    • 104. Hou Q, Li S, Li L, Li Y, Sun X, Tian H. Association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk: a meta-analysis of case–control studies. Medicine (Baltimore) 94(37), e1268 (2015).
    • 105. US FDA. FDA Drug Safety Communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. (2011). https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-restrictions-contraindications-and-dose-limitations-zocor#Simvastatin_Dose_Limitations
    • 106. Wilke RA, Ramsey LB, Johnson SG et al. The Clinical Pharmacogenomics Implementation Consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin. Pharmacol. Ther. 92(1), 112–7 (2012).
    • 107. Bank PCD, Caudle KE, Swen JJ et al. Comparison of the guidelines of the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group. Clin. Pharmacol. Ther. 103(4), 599–618 (2018).
    • 108. Canestaro WJ, Austin MA, Thummel KE. Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genet. Med. 16(11), 810–819 (2014).
    • 109. Soko ND, Masimirembwa C, Dandara C. Pharmacogenomics of rosuvastatin: a glocal (global + local) African perspective and expert review on a statin drug. OMICS 20(9), 498–509 (2016).
    • 110. Umamaheswaran G, Kumar DK, Adithan C. Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters: a review with Indian perspective. Indian J. Med. Res. 139(1), 27–65 (2014).
    • 111. Griese EU, Ilett KF, Kitteringham NR et al. Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in aborigines from western Australia. Pharmacogenetics 11(1), 69–76 (2001).
    • 112. Wiggins BS, Saseen JJ, Page RL II et al. Recommendations for management of clinically significant drug–drug interactions with statins and select agents used in patients with cardiovascular disease. Circulation 134, e1–e28 (2016).
    • 113. Tulner LR, Frankfort SV, Gijsen GJPT, van Campen JPCM, Koks CHW, Beijnen JH. Drug–drug interactions in a geriatric outpatient cohort. Drugs Aging 25(4), 343–355 (2008).
    • 114. Yoon D, Sheen SS, Lee S, Choi YJ, Park RW, Lim H-S. Statins and risk for new-onset diabetes mellitus: a real-world cohort study using a clinical research database. Medicine 95(46), e5429 (2016).
    • 115. Ian Hamilton-Craig. Something you should know about statins and heart disease. (2013). https://theconversation.com/some-things-you-should-know-about-statins-and-heart-disease-19655
    • 116. Zaveri HG, Mansuri SM, Patel VJ. Use of potentially inappropriate medicines in elderly: a prospective study in medicine out-patient department of a tertiary care teaching hospital. Indian J. Pharmacol. 42(2), 95–98 (2010).
    • 117. Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin. Pharmacokinet. 41(5), 343–370 (2002).
    • 118. Gabb GM, Vitry A, Condon A, Limaye V, Alhami G. Serious statin associated myotoxicity and rhabdomyolysis in Aboriginal and Toress Strait Islanders: a case series. Intern. Med. J. 43(9), 987–992 (2013).
    • 119. FDA PI. Statins 2016. http://www.accessdata.fda.gov
    • 120. Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 292, 2585–2590 (2004).
    • 121. Wiggins BS, Saseen JJ, Page RL et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation 134, e468–e495 (2016).
    • 122. Michael BB. Statin safety and drug interactions: clinical implications. Am. J. Cardiol. 97(8), S27–S31 (2006).
    • 123. Stroes ES, Thompson PD, Corsini A et al. Statin-associated muscle symptoms: impact on statin therapy: European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. Eur. Heart J. 36(17), 1012–1022 (2015).
    • 124. Day J, Limaye V. Over-representation of statin-associated necrotising myopathy in patients of Aboriginal and Torres Strait Islander heritage. Intern. Med. J. 48(6), 749–751 (2018).
    • 125. Caughey GE, Gabb GM, Ronson S et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern. Med. 178(9), 1224–1229 (2018).
    • 126. Clark KEN, Isenberg DA. A review of inflammatory idiopathic myopathy focusing on polymyositis. Eur. J. Neurol. 25, 13–23 (2018).
    • 127. Khan NAJ, Khalid S, Ullah S, Malik MU, Makhoul S. Necrotizing autoimmune myopathy: a rare variant of idiopathic inflammatory myopathies. J.Investig. Med. High Impact Case Rep. 5(2), 2324709617709031 (2017).
    • 128. Woolley M, Stebbings S, Highton J. Statin-associated immune-mediated necrotizing myopathy: a New Zealand case series showing possible overrepresentation in Pacific Islanders. Intern. Med. J. 48(1), 32–36 (2018).
    • 129. Nichols L, Pfeifer K, Mammen AL, Shahnoor N, Konersman CG. An unusual case of statin-induced myopathy: anti-HMGCoA necrotizing autoimmune myopathy. J. Gen. Intern. Med. 30(12), 1879–1883 (2015).
    • 130. Dixit A, Abrudescu A. A case of atorvastatin-associated necrotizing autoimmune myopathy, mimicking idiopathic polymyositis. Case Rep.Rheumatol. 2018, 5931046 (2018).
    • 131. Troyanov Y, Landon-Cardinal O, Fritzler MJ et al. Atorvastatin-induced necrotizing autoimmune myositis: an emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype. Medicine 96(3), e5694 (2017).
    • 132. Limaye V, Bundell C, Hollingsworth P et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve 52(2), 196–203 (2015).
    • 133. Mammen AL, Gaudet D, Brisson D et al. Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res. (Hoboken) 64(8), 1233–1237 (2012).
    • 134. Lester S, Cassidy S, Humphreys l et al. Evolution in HLA-DRB1 and major histocompatibility complex class II haplotypes of Australian aborigines definition of a new DRB1 allele and distribution of DRB 1 gene frequencies. Hum. Immunol. 42(2), 154–160 (1995).
    • 135. Gao X, Veale A, Serjeantson SW. HLA class II diversity in Australian aborigines: unusual HLA-DRB 1 alleles. Immunogenetics 36, 333 (1992).
    • 136. Ayo CM, da Silveira Camargo AV, Xavier DH et al. Frequencies of allele groups HLA-A, HLA-B and HLA-DRB1 in a population from the northwestern region of São Paulo State, Brazil. Int. J. Immunogenet. 42(1), 19–25 (2015).
    • 137. Turner RM, Pirmohamed M. Statin-related myotoxicity: a comprehensive review of pharmacokinetic, pharmacogenomic and muscle components. J. Clin. Med. 9, 22 (2020).
    • 138. Rider LG, Shamim E, Okada S et al. Genetic risk and protective factors for idiopathic inflammatory myopathy in Koreans and American whites. Arthritis & Rheumatism 42(6), 1285–1290 (1999).
    • 139. O'Hanlon TP, Rider LG, Mamyrova G et al. HLA polymorphisms in African–Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies. Arthritis & Rheumatism 54(11), 3670–3681 (2006).
    • 140. Wood D, DeBacker G, Faergeman O, Graham I, Mancia G, Pyörälä K. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis 140, 199–270 (1998).
    • 141. Thynne T, Gabb GM. Therapeutic drug safety for Indigenous Australians: how do we close the gap? Med. J. Aust. 204(1), 16–17 (2016).
    • 142. Hayman N. Improving Aboriginal and Torres Strait Islander people’s access to the Pharmaceutical Benefits Scheme. Aust. Prescr. 34, 38–40 (2011).
    • 143. Australian Indigenous Health Info Net. Overview of Australian Aboriginal and Torres Strait Islander health status, 2017 (2018). Available from: https://healthinfonet.ecu.edu.au/learn/health-facts/overview-aboriginal-torres-strait-islander-health-status/