Common genetic variation in the ABCB1 gene is associated with the cholesterol-lowering effect of simvastatin in males

Pharmacogenomics

Volumn 10, Issue 11, 2009, Pages 1743-1751

  Becker, Matthijs L ^a   Visser, Loes E ^a   Van Schaik, Ron H N ^a,b   Hofman, Albert ^a,c   Uitterlinden, André G ^a,c   Stricker, Bruno Hch ^a,c,d  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b STAR Medical Diagnostic Center   (Netherlands)

^c Netherlands Consortium on Healthy Aging   (Netherlands)

^d Drug Safety Unit   (Netherlands)

Author keywords

ABCB1 protein; Cholesterol; Hypercholesterolemia; Male; Pharmacogenetics; Simvastatin

Indexed keywords

ALANINE; CHOLESTEROL; CYSTEINE; GLYCINE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MULTIDRUG RESISTANCE PROTEIN 1; SIMVASTATIN; THREONINE;

ADULT; AGED; ARTICLE; CHOLESTEROL BLOOD LEVEL; COHORT ANALYSIS; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG USE; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; HYPERCHOLESTEROLEMIA; MAJOR CLINICAL STUDY; MALE; PHARMACOGENETICS; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; WILD TYPE;

AGED; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL, LDL; COHORT STUDIES; FEMALE; HAPLOTYPES; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MALE; MIDDLE AGED; P-GLYCOPROTEIN; POLYMORPHISM, SINGLE NUCLEOTIDE; PROSPECTIVE STUDIES; SIMVASTATIN;

EID: 70649106976     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.09.105     Document Type: Article

References (28)

1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344, 1383-1389 (1994).
2. Armitage J: The safety of statins in clinical practice. Lancet 370, 1781-1790 (2007).
3. Sharom FJ: ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics 9, 105-127 (2008).
4. Chinn LW, Kroetz DL: ABCB1 pharmacogenetics: progress, pitfalls, and promise. Clin. Pharmacol. Ther. 81, 265-269 (2007). ■ Describes the role of ABCB1 polymorphisms in clinical practice.
5. Marzolini C, Paus E, Buclin T, Kim RB: Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther. 75, 13-33 (2004). ■ Gives an overview of the effect of ABCB1 polymorphisms on drug response.
6. Cummins CL, Wu CY, Benet LZ: Sex-related differences in the clearance of cytochrome P450 3A4 substrates may be caused by P-glycoprotein. Clin. Pharmacol. Ther. 72, 474-489 (2002). ■ Describes gender differences in P-glycoprotein efflux and CYP3A4 metabolism.
7. Schuetz EG, Furuya KN, Schuetz JD: Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J. Pharmacol. Exp. Ther. 275, 1011-1018 (1995).
8. Chen C, Lin J, Smolarek T, Tremaine L: P-glycoprotein has differential effects on the disposition of statin acid and lactone forms in mdr1a/b knockout and wild-type mice. Drug Metab. Dispos. 35, 1725-1729 (2007).
9. Hochman JH, Pudvah N, Qiu J et al.: Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm. Res. 21, 1686-1691 (2004).
10. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin. Pharmacol. Ther. 80, 565-581 (2006). ■ Gives an overview of the factors influencing the pharmacokinetics of statins.
11. Crettol S, Venetz JP, Fontana M et al.: Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients. Pharmacogenet. Genomics 18, 307-315 (2008).
12. Aarnoudse AJ, Dieleman JP, Visser LE et al.: Common ATP-binding cassette B1 variants are associated with increased digoxin serum concentration. Pharmacogenet. Genomics 18, 299-305 (2008).
13. Aarnoudse AL, van Schaik RH, Dieleman J et al.: MDR1 gene polymorphisms are associated with neuropsychiatric adverse effects of mefloquine. Clin. Pharmacol. Ther. 80, 367-374 (2006).
14. Hofman A, Grobbee DE, de Jong PT, van den Ouweland FA: Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur. J. Epidemiol. 7, 403-422 (1991).
15. Hofman A, Breteler MM, van Duijn CM et al.: The Rotterdam Study: objectives and design update. Eur. J. Epidemiol. 22, 819-829 (2007).
16. Safeer RS, Ugalat PS: Cholesterol treatment guidelines update. Am. Fam. Physician 65, 871-880 (2002).
17. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285, 2486-2497 (2001).
18. Fang Y, van Meurs JB, D'Alesio A et al.: Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am. J. Hum. Genet. 77, 807-823 (2005).
19. Schaid DJ: Evaluating associations of haplotypes with traits. Genet. Epidemiol. 27, 348-364 (2004).
20. Stram DO, Leigh Pearce C, Bretsky P et al.: Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals. Hum. Hered. 55, 179-190 (2003).
21. Benet LZ, Cummins CL, Wy CY: Unmasking the dynamic interplay between efflux transporters and metabolic enzymes. Int. J. Pharm. 277, 3-9 (2004).
22. The SEARCH Collaborative Group: SLCO1B1 variants and statin-induced myopathy - a genomewide study. N. Engl. J. Med. 359, 789-799 (2008).
23. Keskitalo JE, Kurkinen KJ, Neuvonen PJ, Niemi M: ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin. Clin. Pharmacol. Ther. 4, 457-461 (2008).
24. Fiegenbaum M, da Silveira FR, van der Sand C et al.: The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin. Pharmacol. Ther. 78, 551-558 (2005). ■■ ABCB1 haplotypes were previously associated with simvastatin response.
25. Kajinami K, Brousseau ME, Ordovas JM, Schaefer EJ: Polymorphisms in the multidrug resistance-1 (MDR1) gene influence the response to atorvastatin treatment in a gender-specific manner. Am. J. Cardiol. 93, 1046-1050 (2004). ■ ABCB1 haplotypes are also associated with atorvastatin response, although for atorvastatin the effects were stronger in women than in men
26. Thompson JF, Man M, Johnson KJ et al.: An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J. 5, 352-358 (2005).
27. National Center for Biotechnology Information: single nucleotide polymorphism (2008) www.ncbi.nlm.nih.gov/SNP/snp-ref.cgi?locusId=5243 (Accessed 5 September 2008)
28. World Health Organization Collaborating Centre for Drug Statistics Methodology Web site: complete ATC index (2008) www.whocc.no/atcddd (Accessed 28 April 2008)