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Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study

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De Keyser, Catherine E Becker, Matthijs L Uitterlinden, André G Hofman, Albert Lous, Jan J Stricker, Bruno H

Aim: Recently, minor alleles of two strongly linked polymorphisms in the PPARA gene, rs4253728 G>A and rs4823613 A>G, were related to decreased CYP3A4 expression and activity. We studied whether they were associated with the cholesterol-lowering effect of simvastatin. Materials and methods: We identified 123 incident users with cholesterol measurements before and after starting statin therapy in a prospective population-based cohort study. Associations between PPARA polymorphisms and change in total and low-density lipoprotein (LDL)-cholesterol levels were analyzed using linear regression. Results: The minor G allele of the rs4823613 A>G polymorphism was associated with a 0.258 mmol/l (95% CI:-0.470 to-0.046) and a 0.294 mmol/l (95% CI:-0.495 to-0.093) larger reduction in total and LDL-cholesterol, respectively, after starting simvastatin therapy. Results were similar for the rs4253728 G>A polymorphism. Conclusion: The minor alleles of the PPARA rs4253728 and rs4823613 polymorphisms are associated with a better total and LDL-cholesterol-lowering response to simvastatin, possibly through influence on CYP3A4. © 2013 Future Medicine Ltd.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2013
Language Anglais
Journal information "Pharmacogenomics" - Vol. 14, no. 11, p. 1295-1304 (2013)
Peer reviewed yes
Publisher Future Medicine Ltd.
e-issn 1744-8042
issn 1462-2416
Publication status Publié
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  1. Teslovich Tanya M., Musunuru Kiran, Smith Albert V., Edmondson Andrew C., Stylianou Ioannis M., Koseki Masahiro, Pirruccello James P., Ripatti Samuli, Chasman Daniel I., Willer Cristen J., Johansen Christopher T., Fouchier Sigrid W., Isaacs Aaron, Peloso Gina M., Barbalic Maja, Ricketts Sally L., Bis Joshua C., Aulchenko Yurii S., Thorleifsson Gudmar, Feitosa Mary F., Chambers John, Orho-Melander Marju, Melander Olle, Johnson Toby, Li Xiaohui, Guo Xiuqing, Li Mingyao, Shin Cho Yoon, Jin Go Min, Jin Kim Young, Lee Jong-Young, Park Taesung, Kim Kyunga, Sim Xueling, Twee-Hee Ong Rick, Croteau-Chonka Damien C., Lange Leslie A., Smith Joshua D., Song Kijoung, Hua Zhao Jing, Yuan Xin, Luan Jian’an, Lamina Claudia, Ziegler Andreas, Zhang Weihua, Zee Robert Y. L., Wright Alan F., Witteman Jacqueline C. M., Wilson James F., Willemsen Gonneke, Wichmann H.-Erich, Whitfield John B., Waterworth Dawn M., Wareham Nicholas J., Waeber Gérard, Vollenweider Peter, Voight Benjamin F., Vitart Veronique, Uitterlinden Andre G., Uda Manuela, Tuomilehto Jaakko, Thompson John R., Tanaka Toshiko, Surakka Ida, Stringham Heather M., Spector Tim D., Soranzo Nicole, Smit Johannes H., Sinisalo Juha, Silander Kaisa, Sijbrands Eric J. G., Scuteri Angelo, Scott James, Schlessinger David, Sanna Serena, Salomaa Veikko, Saharinen Juha, Sabatti Chiara, Ruokonen Aimo, Rudan Igor, Rose Lynda M., Roberts Robert, Rieder Mark, Psaty Bruce M., Pramstaller Peter P., Pichler Irene, Perola Markus, Penninx Brenda W. J. H., Pedersen Nancy L., Pattaro Cristian, Parker Alex N., Pare Guillaume, Oostra Ben A., O’Donnell Christopher J., Nieminen Markku S., Nickerson Deborah A., Montgomery Grant W., Meitinger Thomas, McPherson Ruth, McCarthy Mark I., McArdle Wendy, Masson David, Martin Nicholas G., Marroni Fabio, Mangino Massimo, Magnusson Patrik K. E., Lucas Gavin, Luben Robert, Loos Ruth J. F., Lokki Marja-Liisa, Lettre Guillaume, Langenberg Claudia, Launer Lenore J., Lakatta Edward G., Laaksonen Reijo, Kyvik Kirsten O., Kronenberg Florian, König Inke R., Khaw Kay-Tee, Kaprio Jaakko, Kaplan Lee M., Johansson Åsa, Jarvelin Marjo-Riitta, Cecile J. W. Janssens A., Ingelsson Erik, Igl Wilmar, Kees Hovingh G., Hottenga Jouke-Jan, Hofman Albert, Hicks Andrew A., Hengstenberg Christian, Heid Iris M., Hayward Caroline, Havulinna Aki S., Hastie Nicholas D., Harris Tamara B., Haritunians Talin, Hall Alistair S., Gyllensten Ulf, Guiducci Candace, Groop Leif C., Gonzalez Elena, Gieger Christian, Freimer Nelson B., Ferrucci Luigi, Erdmann Jeanette, Elliott Paul, Ejebe Kenechi G., Döring Angela, Dominiczak Anna F., Demissie Serkalem, Deloukas Panagiotis, de Geus Eco J. C., de Faire Ulf, Crawford Gabriel, Collins Francis S., Chen Yii-der I., Caulfield Mark J., Campbell Harry, Burtt Noel P., Bonnycastle Lori L., Boomsma Dorret I., Boekholdt S. Matthijs, Bergman Richard N., Barroso Inês, Bandinelli Stefania, Ballantyne Christie M., Assimes Themistocles L., Quertermous Thomas, Altshuler David, Seielstad Mark, Wong Tien Y., Tai E-Shyong, Feranil Alan B., Kuzawa Christopher W., Adair Linda S., Taylor Jr Herman A., Borecki Ingrid B., Gabriel Stacey B., Wilson James G., Holm Hilma, Thorsteinsdottir Unnur, Gudnason Vilmundur, Krauss Ronald M., Mohlke Karen L., Ordovas Jose M., Munroe Patricia B., Kooner Jaspal S., Tall Alan R., Hegele Robert A., Kastelein John J.P., Schadt Eric E., Rotter Jerome I., Boerwinkle Eric, Strachan David P., Mooser Vincent, Stefansson Kari, Reilly Muredach P., Samani Nilesh J, Schunkert Heribert, Cupples L. Adrienne, Sandhu Manjinder S., Ridker Paul M, Rader Daniel J., van Duijn Cornelia M., Peltonen Leena, Abecasis Gonçalo R., Boehnke Michael, Kathiresan Sekar, Biological, clinical and population relevance of 95 loci for blood lipids, 10.1038/nature09270
  2. Williams David, Feely John, Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors : , 10.2165/00003088-200241050-00003
  3. Hansten Philip D, Possible risks to patients receiving statins combined with other medications, 10.1016/s0735-1097(02)02815-2
  4. Thomas M., Burk O., Klumpp B., Kandel B. A., Damm G., Weiss T. S., Klein K., Schwab M., Zanger U. M., Direct Transcriptional Regulation of Human Hepatic Cytochrome P450 3A4 (CYP3A4) by Peroxisome Proliferator-Activated Receptor Alpha (PPAR ), 10.1124/mol.112.082503
  5. Hu Miao, Mak Valiant WL, Xiao Yajie, Tomlinson Brian, Associations between the genotypes and phenotype of CYP3A and the lipid response to simvastatin in Chinese patients with hypercholesterolemia, 10.2217/pgs.12.181
  6. Flavell D. M., Peroxisome Proliferator-Activated Receptor alpha Gene Variants Influence Progression of Coronary Atherosclerosis and Risk of Coronary Artery Disease, 10.1161/01.cir.0000012145.80593.25
  7. Vohl, J. Lipid Res., 41, 945 (2000)
  8. Tai E.S., Association Between the PPARA L162V Polymorphism and Plasma Lipid Levels: The Framingham Offspring Study, 10.1161/01.atv.0000012302.11991.42
  9. Jamshidi Y., Peroxisome Proliferator-Activated Receptor alpha Gene Regulates Left Ventricular Growth in Response to Exercise and Hypertension, 10.1161/hc0802.104535
  10. Flavell D. M., Torra I. Pineda, Jamshidi Y., Evans D., Diamond J. R., Elkeles R. S., Bujac S. R., Miller G., Talmud P. J., Staels B., Humphries S. E., Variation in the PPARα gene is associated with altered function in vitro and plasma lipid concentrations in Type II diabetic subjects, 10.1007/s001250051357
  11. Reinhard Wibke, Stark Klaus, Sedlacek Kamil, Fischer Marcus, Baessler Andrea, Neureuther Katharina, Weber Stefan, Kaess Bernhard, Wiedmann Silke, Mitsching Stefan, Lieb Wolfgang, Erdmann Jeanette, Meisinger Christa, Doering Angela, Tolle Ralf, Jeron Andreas, Riegger Guenter, Hengstenberg Christian, Association betweenPPARα gene polymorphisms and myocardial infarction, 10.1042/cs20070391
  12. Shin Min-Jeong, Kanaya Alka M., Krauss Ronald M., Polymorphisms in the peroxisome proliferator activated receptor α gene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians, 10.1016/j.atherosclerosis.2007.10.004
  13. Wahli Walter, Kersten Sander, Desvergne Béatrice, 10.1038/35013000
  14. Fruchart Jean-Charles, Duriez Patrick, Staels Bart, Peroxisome proliterator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis : , 10.1097/00041433-199906000-00007
  15. Fruchart Jean-Charles, Peroxisome proliferator-activated receptor-alpha (PPARα): At the crossroads of obesity, diabetes and cardiovascular disease, 10.1016/j.atherosclerosis.2009.03.008
  16. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HAP, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD, Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study, 10.1016/s0140-6736(08)60599-1
  17. Miller S.A., Dykes D.D., Polesky H.F., A simple salting out procedure for extracting DNA from human nucleated cells, 10.1093/nar/16.3.1215
  18. Hofman Albert, van Duijn Cornelia M., Franco Oscar H., Ikram M. Arfan, Janssen Harry L. A., Klaver Caroline C. W., Kuipers Ernst J., Nijsten Tamar E. C., Stricker Bruno H. Ch., Tiemeier Henning, Uitterlinden André G., Vernooij Meike W., Witteman Jacqueline C. M., The Rotterdam Study: 2012 objectives and design update, 10.1007/s10654-011-9610-5
  19. Hofman A., Grobbee D. E., De Jong P. T. V. M., Van den Ouweland F. A., Determinants of disease and disability in the elderly: The Rotterdam elderly study, 10.1007/bf00145007
  20. Klein Kathrin, Thomas Maria, Winter Stefan, Nussler Andreas K., Niemi Mikko, Schwab Matthias, Zanger Ulrich M., PPARA: A Novel Genetic Determinant of CYP3A4 In Vitro and In Vivo, 10.1038/clpt.2011.336
  21. Zeigler-Johnson Charnita, Friebel Tara, Walker Amy H., Wang Yiting, Spangler Elaine, Panossian Saarene, Patacsil Margerie, Aplenc Richard, Wein Alan J., Malkowicz S. Bruce, Rebbeck Timothy R., CYP3A4,CYP3A5, andCYP3A43Genotypes and Haplotypes in the Etiology and Severity of Prostate Cancer, 10.1158/0008-5472.can-04-1651
  22. Miao J, Jin Y, Marunde R L, Kim S, Quinney S, Radovich M, Li L, Hall S D, Association of genotypes of the CYP3A cluster with midazolam disposition in vivo, 10.1038/tpj.2009.21
  23. Kuehl Peter, Zhang Jiong, Lin Yvonne, Lamba Jatinder, Assem Mahfoud, Schuetz John, Watkins Paul B., Daly Ann, Wrighton Steven A., Hall Stephen D., Maurel Patrick, Relling Mary, Brimer Cynthia, Yasuda Kazuto, Venkataramanan Raman, Strom Stephen, Thummel Kenneth, Boguski Mark S., Schuetz Erin, 10.1038/86882
  24. Kivist?? Kari T, Niemi Mikko, Schaeffeler Elke, Pitk??l?? Kaisu, Tilvis Reijo, Fromm Martin F, Schwab Matthias, Eichelbaum Michel, Strandberg Timo, Lipid-lowering response to statins is affected by CYP3A5 polymorphism : , 10.1097/01.fpc.0000114762.78957.a5
  25. Kim Kyoung-Ah, Park Pil-Whan, Lee Ock-Je, Kang Dong-Kyun, Park Ji-Young, Effect of PolymorphicCYP3A5Genotype on the Single-Dose Simvastatin Pharmacokinetics in Healthy Subjects, 10.1177/0091270006295063
  26. Becker Matthijs L., Visser Loes E., van Schaik Ron H. N., Hofman Albert, Uitterlinden André G., Ch. Stricker Bruno H., Influence of genetic variation inCYP3A4andABCB1on dose decrease or switching during simvastatin and atorvastatin therapy, 10.1002/pds.1866
  27. Kajinami Kouji, Brousseau Margaret E, Ordovas Jose M, Schaefer Ernst J, CYP3A4 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin in primary hypercholesterolemia, 10.1016/j.amjcard.2003.08.078
  28. Elens Laure, Becker Matthijs L., Haufroid Vincent, Hofman Albert, Visser Loes E., Uitterlinden André G., Stricker Bruno Ch., van Schaik Ron H.N., Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in The Rotterdam Study : , 10.1097/fpc.0b013e32834c6edb
  29. Wang D, Guo Y, Wrighton S A, Cooke G E, Sadee W, Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs, 10.1038/tpj.2010.28
  30. Prueksaritanont Thomayant, Ma Bennett, Yu Nathan, The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6 : Simvastatin hydroxy acid metabolism is mediated by CYP3A, 10.1046/j.1365-2125.2003.01833.x
  31. Prueksaritanont, Drug Metab. Dispos., 25, 1191 (1997)
  32. Vickers, Drug Metab. Dispos., 18, 476 (1990)
  33. Neuvonen Pertti J, Backman Janne T, Niemi Mikko, Pharmacokinetic Comparison of the Potential Over-the-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin : , 10.2165/00003088-200847070-00003
  34. Zineh Issam, Johnson Julie A, Pharmacogenetics of chronic cardiovascular drugs: applications and implications, 10.1517/14656566.7.11.1417
  35. Schmitz Gerd, Drobnik Wolfgang, Pharmacogenomics and Pharmacogenetics of Cholesterol-Lowering Therapy, 10.1515/cclm.2003.088
  36. Shitara Yoshihisa, Sugiyama Yuichi, 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, 10.1016/j.pharmthera.2006.03.003
  37. Mangravite, Curr. Opin. Mol. Ther., 10, 555 (2008)
  38. Mangravite, Curr. Opin. Lipidol., 18, 409 (2007)
  39. Yan Andrew T., Yan Raymond T., Tan Mary, Hackam Daniel G., Leblanc Kori L., Kertland Heather, Tsang Jennifer L., Jaffer Shahin, Kates Martin L., Leiter Lawrence A., Fitchett David H., Langer Anatoly, Goodman Shaun G., Contemporary Management of Dyslipidemia in High-Risk Patients: Targets Still Not Met, 10.1016/j.amjmed.2005.11.015
  40. Davidson Michael H., Maki Kevin C., Pearson Thomas A., Pasternak Richard C., Deedwania Prakash C., McKenney James M., Fonarow Gregg C., Maron David J., Ansell Benjamin J., Clark Luther T., Ballantyne Christie M., Results of the National Cholesterol Education (NCEP) Program Evaluation Project Utilizing Novel E-Technology (NEPTUNE) II Survey and Implications for Treatment Under the Recent NCEP Writing Group Recommendations, 10.1016/j.amjcard.2005.04.019
  41. Grundy S. M., Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines, 10.1161/01.cir.0000133317.49796.0e
  42. Cheng Alice YY, Leiter Lawrence A, Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines : , 10.1097/01.hco.0000231412.15049.fb
  43. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial, 10.1016/s0140-6736(02)09327-3
  44. Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels, 10.1056/nejm199811053391902
  45. Shepherd James, Cobbe Stuart M., Ford Ian, Isles Christopher G., Lorimer A. Ross, Macfarlane Peter W., McKillop James H., Packard Christopher J., Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia, 10.1056/nejm199511163332001
  46. Tuomilehto J., Vidgren G., Toivanen L., Tuomilehto-Wolf E., Kohtamaki K., Stengård J., Zimmet P., Mackay I.R., Rowley Mj, Koskela P., Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease, 10.1016/s0140-6736(94)92521-6
Bibliographic reference De Keyser, Catherine E ; Becker, Matthijs L ; Uitterlinden, André G ; Hofman, Albert ; Lous, Jan J ; et. al. Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study. In: Pharmacogenomics, Vol. 14, no. 11, p. 1295-1304 (2013)
Permanent URL http://hdl.handle.net/2078.1/160705