The rs13064411 polymorphism in the WDR52 gene, associated with PCSK9 levels, modifies statin-induced changes in serum total and LDL cholesterol levels

Pharmacogenetics and Genomics

Volumn 25, Issue 3, 2015, Pages 134-142

  De Keyser, Catherine E ^a,c   Becker, Matthijs L ^a,e   Hofman, Albert ^a   Lous, Jan J ^b   Uitterlinden, André G ^a   Visser, Loes E ^a,d   Stricker, Bruno H ^a,c  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b STAR Medical Diagnostic Center   (Netherlands)

^c Inspectorate of Health Care   (Netherlands)

^d Clinical Pharmacy   (Netherlands)

^e Pharmacy Foundation of Haarlem Hospitals   (Netherlands)

Author keywords

cholesterol; HMG CoA reductase inhibitors; PCSK9; pharmacogenetics; rs13064411

Indexed keywords

ATORVASTATIN; CHOLESTEROL; FLUINDOSTATIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; KEXIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PRAVASTATIN; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; ROSUVASTATIN; SERINE PROTEINASE; SIMVASTATIN; SUBTILISIN; UNCLASSIFIED DRUG; HYPOCHOLESTEROLEMIC AGENT; LOW DENSITY LIPOPROTEIN RECEPTOR; NUCLEAR PROTEIN; PCSK9 PROTEIN, HUMAN; PROTEIN; WDR52 PROTEIN, HUMAN;

AGED; ALLELE; ARTICLE; CHOLESTEROL BLOOD LEVEL; COHORT ANALYSIS; CONTROLLED STUDY; FEMALE; FOLLOW UP; GENE; GENE FREQUENCY; GENOTYPE; HETEROZYGOTE; HUMAN; MAJOR CLINICAL STUDY; MALE; POPULATION BASED CASE CONTROL STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; SENSITIVITY ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; WDR52 GENE; BLOOD; GENETIC POLYMORPHISM; GENETICS; METABOLISM; MIDDLE AGED; SEXUAL DEVELOPMENT;

AGED; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL, LDL; FEMALE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MALE; MIDDLE AGED; NUCLEAR PROTEINS; POLYMORPHISM, GENETIC; PROPROTEIN CONVERTASES; PROSPECTIVE STUDIES; PROTEINS; RECEPTORS, LDL; SERINE ENDOPEPTIDASES; SEX CHARACTERISTICS;

EID: 84923223103     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0000000000000120     Document Type: Article

References (47)

1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383-1389.
2. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333:1301-1307.
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339:1349-1357.
4. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7-22.
5. Mangravite LM, Krauss RM. Pharmacogenomics of statin response. Curr Opin Lipidol 2007; 18:409-414.
6. Mangravite LM, Wilke RA, Zhang J, Krauss RM. Pharmacogenomics of statin response. Curr Opin Mol Ther 2008; 10:555-561.
7. Schmitz G, Schmitz-Madry A, Ugocsai P. Pharmacogenetics and pharmacogenomics of cholesterol-lowering therapy. Curr Opin Lipidol 2007; 18:164-173.
8. Donnelly LA, Palmer CN, Whitley AL, Lang CC, Doney AS, Morris AD, et al. Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study. Pharmacogenet Genomics 2008; 18:279-287.
9. Kobayashi T, Homma Y. Effects of low-dose pravastatin on plasma levels of lipids and apolipoproteins in Japanese type II hyperlipoproteinemic subjects with apolipoprotein E phenotype E3/2, E3/3, and E4/3. J Clin Pharmacol 2001; 41:1055-1058.
10. Thompson JF, Man M, Johnson KJ, Wood LS, Lira ME, Lloyd DB, et al. An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J 2005; 5:352-358.
11. Nestel P, Simons L, Barter P, Clifton P, Colquhoun D, Hamilton-Craig I, et al. A comparative study of the efficacy of simvastatin and gemfibrozil in combined hyperlipoproteinemia: prediction of response by baseline lipids, apo E genotype, lipoprotein(a) and insulin. Atherosclerosis 1997; 129:231-239.
12. Maitland-van der Zee AH, Jukema JW, Zwinderman AH, Hallman DM, De Boer A, Kastelein JJ, et al. Apolipoprotein-E polymorphism and response to pravastatin in men with coronary artery disease (REGRESS). Acta Cardiol 2006; 61:327-331.
13. Thompson JF, Hyde CL, Wood LS, Paciga SA, Hinds DA, Cox DR, et al. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ Cardiovasc Genet 2009; 2:173-181.
14. Postmus I, Trompet S, Deshmukh HA, Barnes MR, Li X, Warren HR, et al. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat Commun 2014; 5:5068.
15. Farnier M. PCSK9: from discovery to therapeutic applications. Arch Cardiovasc Dis 2014; 107:58-66.
16. Urban D, Poss J, Bohm M, Laufs U. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 2013; 62:1401-1408.
17. Lo Surdo P, Bottomley MJ, Calzetta A, Settembre EC, Cirillo A, Pandit S, et al. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep 2011; 12:1300-1305.
18. Alborn WE, Cao G, Careskey HE, Qian YW, Subramaniam DR, Davies J, et al. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem 2007; 53:1814-1819.
19. Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res 2010; 51:2714-2721.
20. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab 2009; 94:2537-2543.
21. Mayne J, Raymond A, Chaplin A, Cousins M, Kaefer N, Gyamera- Acheampong C, et al. Plasma PCSK9 levels correlate with cholesterol in men but not in women. Biochem Biophys Res Commun 2007; 361:451-456.
22. Careskey HE, Davis RA, Alborn WE, Troutt JS, Cao G, Konrad RJ. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008; 49:394-398.
23. Mayne J, Dewpura T, Raymond A, Cousins M, Chaplin A, Lahey KA, et al. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids Health Dis 2008; 7:22.
24. Awan Z, Seidah NG, MacFadyen JG, Benjannet S, Chasman DI, Ridker PM, et al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial. Clin Chem 2012; 58:183-189.
25. Berthold HK, Seidah NG, Benjannet S, Gouni-Berthold I. Evidence from a randomized trial that simvastatin, but not ezetimibe, upregulates circulating PCSK9 levels. PLoS One 2013; 8:e60095.
26. Guo YL, Liu J, Xu RX, Zhu CG, Wu NQ, Jiang LX, et al. Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9. Clin Drug Investig 2013; 33:877-883.
27. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med 2012; 366:1108-1118.
28. Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet 2012; 380:29-36.
29. Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012; 308:2497-2506.
30. Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebocontrolled, dose-ranging, phase 2 study. Lancet 2012; 380:2007-2017.
31. Theusch E, Medina MW, Rotter JI, Krauss RM. Ancestry and other genetic associations with plasma PCSK9 response to simvastatin. Pharmacogenet Genomics 2014; 24:492-500.
32. Hofman A, Darwish Murad S, van Duijn CM, Franco OH, Goedegebure A, Ikram MA, et al. The Rotterdam Study: 2014 objectives and design update. Eur J Epidemiol 2013; 28:889-926.
33. Hofman A, Grobbee DE, de Jong PTVM, van den Ouweland FA. Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol 1991; 7:403-422.
34. Complete ATC index 2010. WHO collaborating centre for drugs statistics methodology web site. Available at: http://www.whocc.no/atc-ddd-index. [Accessed 17 August 2014].
35. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16:1215.
36. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 2008; 371:1505-1512.
37. Avery CL, Der JS, Whitsel EA, Sturmer T. Comparison of study designs used to detect and characterize pharmacogenomic interactions in nonexperimental studies: a simulation study. Pharmacogenet Genomics 2014; 24:146-155.
38. Seidah NG. PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets 2009; 13:19-28.
39. Berge KE, Ose L, Leren TP. Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler Thromb Vasc Biol 2006; 26:1094-1100.
40. Jeong HJ, Lee HS, Kim KS, Kim YK, Yoon D, Park SW. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res 2008; 49:399-409.
41. Khera A. Statins, plasma proprotein convertase subtilisin/kexin type 9 concentrations, and LDL lowering. Clin Chem 2012; 58:6-7.
42. Li D, Roberts R. WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci 2001; 58:2085-2097.
43. Smith TF, Gaitatzes C, Saxena K, Neer EJ. The WD repeat: a common architecture for diverse functions. Trends Biochem Sci 1999; 24:181-185.
44. Zhang DW, Garuti R, Tang WJ, Cohen JC, Hobbs HH. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci USA 2008; 105:13045-13050.
45. Smith PM, Cowan A, White BA. The low-density lipoprotein receptor is regulated by estrogen and forms a functional complex with the estrogen-regulated protein ezrin in pituitary GH3 somatolactotropes. Endocrinology 2004; 145:3075-3083.
46. Croston GE, Milan LB, Marschke KB, Reichman M, Briggs MR. Androgen receptor-mediated antagonism of estrogen-dependent low density lipoprotein receptor transcription in cultured hepatocytes. Endocrinology 1997; 138:3779-3786.
47. Penning-van Beest FJ, Termorshuizen F, Goettsch WG, Klungel OH, Kastelein JJ, Herings RM. Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study. Eur Heart J 2007; 28:154-159.