High-density lipoprotein (HDL) cholesterol: Leveraging practice-based biobank cohorts to characterize clinical and genetic predictors of treatment outcome

Pharmacogenomics Journal

Volumn 11, Issue 3, 2011, Pages 162-173

  Wilke, R A ^a  

^a VANDERBILT UNIVERSITY   (United States)

Author keywords

dyslipidemia; eMERGE network; obesity; PGRN network

Indexed keywords

ABC TRANSPORTER A1; APOLIPOPROTEIN A1; APOLIPOPROTEIN A2; ATORVASTATIN; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ESTER TRANSFER PROTEIN; ENDOCANNABINOID; EZETIMIBE; FENOFIBRATE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; NICOTINIC ACID; SCAVENGER RECEPTOR BI; TORCETRAPIB;

ATHEROGENESIS; CARDIOVASCULAR DISEASE; CATABOLISM; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; CHOLESTEROL TRANSPORT; CLINICAL PRACTICE; CORONARY ARTERY DISEASE; DRUG ACTIVITY; DRUG EFFICACY; ENZYME ACTIVITY; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC VARIABILITY; HEART INFARCTION; HOMEOSTASIS; HUMAN; HYDROLYSIS; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIPID METABOLISM; MOLECULAR DYNAMICS; OUTCOME ASSESSMENT; OXIDATION; PARTICLE SIZE; PHARMACOGENOMICS; PRIORITY JOURNAL; PROCESS OPTIMIZATION; PROTEIN STABILITY; PROTEIN SYNTHESIS; PROTEOMICS; QUANTITATIVE TRAIT LOCUS; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION;

APOLIPOPROTEIN A-I; CHOLESTEROL, HDL; CHOLESTEROL, LDL; DATABASES, NUCLEIC ACID; DOSE-RESPONSE RELATIONSHIP, DRUG; DYSLIPIDEMIAS; ELECTRONIC HEALTH RECORDS; GENETIC ASSOCIATION STUDIES; GENETIC MARKERS; HEPTANOIC ACIDS; HUMANS; OBESITY; PRAVASTATIN; PYRROLES; RISK ASSESSMENT; SIMVASTATIN; TREATMENT OUTCOME;

EID: 79957501024     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2010.86     Document Type: Review

References (112)

1. Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 2009; 10: 109-121.
2. Rader DJ. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med 2007; 120: S12-S18.
3. Goodarzi MO, Taylor KD, Scheuner MT, Antoine HJ, Guo X, Shah PK et al. Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts. Pharmacogenomics J 2007; 7: 66-73. (Pubitemid 46322081)
4. Krauss RM. Is the size of low-density lipoprotein particles related to the risk of coronary heart disease? JAMA 2002; 287: 712-713. (Pubitemid 34250450)
5. Rubin EM, Krauss RM, Spangler EA, Verstuyft JG, Clift SM. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 1991; 353: 265-267. (Pubitemid 21896769)
6. 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: Adult Treatment Panel III). 2001; 285: 2486-2497.
7. Tall AR. CETP inhibitors to increase HDL cholesterol levels. N Engl J Med 2007; 356: 1364-1366. (Pubitemid 46513305)
8. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 2005; 96: 1221-1232. (Pubitemid 40962099)
9. Sahoo D, Darlington YF, Pop D, Williams DL, Connelly MA. Scavenger receptor class B type I (SR-BI) assembles into detergent-sensitive dimers and tetramers. Biochim Biophys Acta 2007; 1771: 807-817. (Pubitemid 46891297)
10. Thuren T, Weisgraber KH, Sisson P, Waite M. Role of apolipoprotein E in hepatic lipase catalyzed hydrolysis of phospholipid in high-density lipoproteins. Biochemistry 1992; 231: 2332-2338.
11. Després JP, Ferland M, Moorjani S, Nadeau A, Tremblay A, Lupien PJ et al. Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. Arteriosclerosis 1989; 9: 485-492. (Pubitemid 19184483)
12. Rashid S, Watanabe T, Sakaue T, Lewis GF. Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. Clin Biochem 2003; 36: 421-429. (Pubitemid 37083556)
13. Rader DJ. of reverse cholesterol transport and clinical implications. Am J Cardiol 2003; 92(4A): 42J-49J.
14. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007; 356: 1304-1316. (Pubitemid 46513296)
15. Soro-Paavonen A, Naukkarinen J, Lee-Rueckert M, Watanabe H, Rantala E, Soderlund S et al. Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDL. J Lipid Res 2007; 48: 1409-1416. (Pubitemid 47312044)
16. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 1996; 276: 875-881. (Pubitemid 26301606)
17. Bittner V. Perspectives on dyslipidemia and coronary heart disease in women. J Am Coll Cardiol 2005; 46: 1628-1635. (Pubitemid 41531614)
18. Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA 2005; 294: 326-333. (Pubitemid 41043776)
19. Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006; 83: 1025-1031. (Pubitemid 44713100)
20. Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring) 2008; 16: 2323-2330.
21. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-952. (Pubitemid 39208455)
22. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 2000; 97: 14478-14483. (Pubitemid 32016601)
23. Ashen MD, Blumenthal RS. Clinical practice-low HDL cholesterol levels. N Engl J Med 2005; 353: 1252-1260. (Pubitemid 41345947)
24. 0homme D, Tremblay A, Nadeau A, Couillard C et al. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J Lipid Res 2001; 42: 2007-2014. (Pubitemid 34001049)
25. Navab M, Hama SY, Anantharamaiah GM, Hassan K, Hough GP, Watson AD et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J Lipid Res 2000; 41: 1495-1508.
26. Kontush A, Chapman MJ. Functionally defective high-density lipopro-tein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol Rev 2006; 58: 342-374. (Pubitemid 44394906)
27. Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43: 1363-1379.
28. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752. (Pubitemid 41532612)
29. Lusis AJ, Attie AD, Reue K. Metabolic syndrome: from epidemiology to systems biology. Nat Rev Genet 2008; 9: 819-830.
30. Brunzell JD, Hazzard WR, Porte Jr D, Bierman EL. Evidence for a common, saturable, triglyceride removal mechanism for chylomicrons and very low density lipoproteins in man. J Clin Invest 1973; 52: 1578-1585.
31. Jansen H, Breedveld B, Schoonderwoerd K. Role of lipoprotein lipases in postprandial lipid metabolism. Atherosclerosis 1998; 14(Suppl 1): S31-S34.
32. Reaven G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation 2002; 106: 286-288. (Pubitemid 34778947)
33. Glaser DS, Yost TJ, Eckel RH. Preheparin lipoprotein lipolytic activities: relationship to plasma lipoproteins and postheparin lipolytic activities. J Lipid Res 1992; 33: 209-214.
34. Eckel RH, Yost TJ, Jensen DR. Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase. Eur J Clin Invest 1995; 25: 396-402.
35. Merkel M, Eckel RH, Goldberg IJ. Lipoprotein lipase: genetics, lipid uptake, and regulation. J Lipid Res 2002; 43: 1997-2006. (Pubitemid 35471065)
36. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M et al. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999; 22: 336-345. (Pubitemid 29369523)
37. Scheen AJ, Paquot N. Use of cannabinoid CB1 receptor antagonists for the treatment of metabolic disorders. Best Pract Res Clin Endocrinol Metab 2009; 23: 103-116.
38. Howlett AC. The cannabinoid receptors. Prostaglandins Other Lipid Mediat 2002; 68-69: 619-631. (Pubitemid 35247425)
39. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389-1397. (Pubitemid 40523733)
40. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761-775. (Pubitemid 43244304)
41. Van Gaal L, Pi-Sunyer X, Després JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care 2008; 31 (Suppl 2): S229-S240.
42. Wangensteen T, Akselsen H, Holmen J, Undlien D, Retterstøl L. A common haplotype in NAPEPLD is associated with severe obesity in a Norwegian population-based cohort (the HUNT Study). Obesity 2010 (E-pub ahead of print 30 September 2010).
43. Baye TM, Zhang Y, Smith E, Hillard CJ, Gunnell J, Myklebust J et al. Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics 2008; 9: 1647-1656.
44. Zhang Y, Sonnenberg G, Baye TM, Littrell J, Gunnell J, DeLaForest A et al. Genetic variation in fatty acid amide hydrolase (FAAH) is associated with obesity-related dyslipidemia, independent of insulin responsiveness, in multigenerational families of Northern European descent. Pharmacogenomics 2009; 10: 1929-1939.
45. Goldstein DB. Common genetic variation and human traits. N Engl J Med 2009; 360: 1696-1698.
46. Li B, Leal SM. Discovery of rare variants via sequencing: implications for the design of complex trait association studies. PLoS Genet 2009; 5: e1000481.
47. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008; 40: 189-197. (Pubitemid 351171402)
48. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 2008; 40: 161-169. (Pubitemid 351171403)
49. Barber MJ, Mangravite LM, Hyde CL, Chasman D, Smith J, McCarty CA et al. Genome-wide association of lipid-lowering response to statins in combined study populations. PLoS One 2010; 5: e9763.
50. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010; 466: 707-713.
51. Wilke RA, Mareedu RK, Moore JH. The pathway less traveled-moving from candidate genes to candidate pathways in the analysis of genome-wide data from large scale pharmacogenetic association studies. Curr Pharmacogenomics Person Med 2008; 6: 150-159.
52. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results: I reduction in incidence of coronary heart disease. JAMA 1984; 251: 351-364.
53. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary artery disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.
54. 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. New Engl J Med 1995; 333: 1301-1307.
55. Yee HS, Fong NT. Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Ann Pharmacother 1998; 32: 1030-1043. (Pubitemid 28498464)
56. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195-2207.
57. Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov 2003; 2: 517-526. (Pubitemid 37361744)
58. Kinley S. What do we know about plieotropic effects? Lipid letter 2005; 4: 1.
59. Asztalos BF, Horvath KV, McNamara JR, Roheim PS, Rubinstein JJ, Schaefer EJ. Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients. Atherosclerosis 2002; 164: 361-369. (Pubitemid 35223088)
60. Schaefer EJ, Asztalos BF. The effects of statins on high-density lipoproteins. Curr Atheroscler Rep 2006; 8: 41-49. (Pubitemid 43675754)
61. Wierzbicki AS, Mikhailidis DP. Dose-response effect of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholester-olaemic patients: a review of five comparative studies. Int J Cardiol 2002; 84: 53-57. (Pubitemid 34718090)
62. Altmann SW, Davis Jr HR, Zhu LJ, Yao X, Hoos LM, Tetzloff G et al. Niemann-pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 2004; 303: 1201-1204. (Pubitemid 38233587)
63. Van Heek M, France CF, Compton DS, McLeod RL, Yumibe NP, Alton KB et al. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997; 283: 157-163. (Pubitemid 27438958)
64. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S et al. Identification of human UDP-glucuronosyltransfer-ase enzyme(s) responsible for the glucuronidation of ezetimibe (zetia). Drug Metab Dispos 2004; 32: 314-320. (Pubitemid 38263889)
65. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005; 44: 467-494. (Pubitemid 40733733)
66. Patrick JE, Kosoglou T, Stauber KL, Alton KB, Maxwell SE, Zhu Y et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos 2002; 30: 430-437. (Pubitemid 34263828)
67. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholes-terolemia. Am J Cardiol 2002; 90: 1092-1097. (Pubitemid 35335597)
68. Dujovne CA, Suresh R, McCrary SC, Maccubbin D, Strony J, Veltri E. Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years. Int J Clin Pract 2008; 62: 1332-1336.
69. Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A et al. Ezetimibe monotherapy for cholesterol lowering in 2722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med 2009; 265: 568-580.
70. Venero CV, Venero JV, Seip RL, Thompson PD. Effectiveness of thrice weekly ezetimibe. Am J Cardiol 2008; 102: 1205-1206.
71. Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J 2003; 24: 729-741. (Pubitemid 36458985)
72. Sudhop T, Reber M, Tribble D, Sapre A, Taggart W, Gibbons P et al. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. J Lipid Res 2009; 50: 2117-2123.
73. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359: 1343-1356.
74. Califf RM, Robert AH, Michael AB. Premature release of data from clinical trials of ezetimibe. N Engl J Med 2009; 361: 7.
75. Devine PJ, Turco MA, Taylor AJ. Design and rationale of the ARBITER 6 trial (arterial biology for the investigation of the treatment effects of reducing cholesterol)-6-HDL and LDL treatment strategies in atherosclerosis (HALTS). Cardiovasc Drugs Ther 2007; 21: 221-225. (Pubitemid 46817479)
76. Kastelein JJ, Van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007; 356: 1620-1630. (Pubitemid 46631671)
77. Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE. Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (investigation of lipid level management using coronary ultrasound to assess reduction of atherosclerosis by CETP inhibition and HDL elevation). Circulation 2008; 118: 2506-2514.
78. Nagano M, Yamashita S, Hirano K, Takano M, Maruyama T, Ishihara M et al. Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese. J Atheroscler Thromb 2004; 11: 110-121.
79. Rhyne J, Ryan MJ, White C, Chimonas T, Miller M. The two novel CETP mutations Gln87X and Gln165X in a compound heterozygous state are associated with marked hyperalphalipoproteinemia and absence of significant coronary artery disease. J Mol Med 2006; 84: 647-650. (Pubitemid 44162554)
80. Wolk R, Chen D, Clark RW, Mancuso J, Barclay PL. Pharmacokinetic, pharmacodynamic, and safety profile of a new cholesteryl ester transfer protein inhibitor in healthy human subjects. Clin Pharmacol Ther 2009; 86: 430-437.
81. Hampton T. New clues to HDL's benefits revealed. JAMA 2007; 297: 1537. (Pubitemid 46588385)
82. Reilly MP, Tall AR. HDL proteomics: pot of gold or Pandora's box? J Clin Invest 2007; 117: 595-598. (Pubitemid 46348516)
83. Vaisar T, Pennathur S, Green PS, Gharib SA, Hoofnagle AN, Cheung MC et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J Clin Invest 2007; 117: 746-756. (Pubitemid 46348533)
84. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998; 98: 2088-2093. (Pubitemid 28512236)
85. Fruchart JC. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 2009; 205: 1-8.
86. Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999; 354: 141-148. (Pubitemid 29313157)
87. Shulman AI, Mangelsdorf DJ. Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med 2005; 353: 604-615. (Pubitemid 41138942)
88. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366: 1849-1861.
89. Brown WV, Dujovne CA, Farquhar JW, Feldman EB, Grundy SM, Knopp RH et al. Effects of fenofibrate on plasma lipids. Double-blind, multicenter study in patients with type IIA or IIB hyperlipidemia. Arteriosclerosis 1986; 6: 670-678. (Pubitemid 17190167)
90. Genest Jr J, Nguyen NH, Theroux P, Davignon J, Cohn JS. Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. J Cardiovasc Pharmacol 2000; 35: 164-172. (Pubitemid 30032909)
91. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317: 1237-1245. (Pubitemid 17147964)
92. Tenkanen L, Mänttäri M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. Circulation 1995; 92: 1779-1785.
93. Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from framingham to the veterans affairs high-density lipoprotein intervention trial. Am J Cardiol 2000; 86: 19L-22L.
94. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410-418. (Pubitemid 29362514)
95. Meyers CD, Kamanna VS, Kashyap ML. Niacin therapy in atherosclerosis. Curr Opin Lipidol 2004; 15: 659-665. (Pubitemid 39612984)
96. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol 2008; 101(8A): 20B-26B.
97. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 2003; 9: 352-355. (Pubitemid 36362793)
98. Plaisance EP, Lukasova M, Offermanns S, Zhang Y, Cao G, Judd RL. Stimulates adiponectin secretion through the GPR109A receptor. Am J Physiol Endocrinol Metab 2009; 296: E549-E558.
99. Zhang Y, Schmidt RJ, Foxworthy P, Emkey R, Oler JK, Large TH et al. Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Biochem Biophys Res Commun 2005; 334: 729-732. (Pubitemid 40982427)
100. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004; 110: 3512-3517. (Pubitemid 39612564)
101. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2008; 51: 724-730. (Pubitemid 351221217)
102. Lamon-Fava S, Asztalos BF, Howard TD, Reboussin DM, Horvath KV, Schaefer EJ et al. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clin Endocrinol (Oxf) 2010; 72: 169-175.
103. Wilke RA, Berg RL, Linneman JG, Peissig P, Starren J, Ritchie MD et al. Quantification of the clinical modifiers impacting high density lipoprotein (HDL) cholesterol in the community-Personalized Medicine Research Project (PMRP). Prev Cardiol 2010; 13: 63-68.
104. Carroll MD, Lacher DA, Sorlie PD, Cleeman JI, Gordon DJ, Wolz M et al. Trends in serum lipids and lipoproteins of adults, 1960-2002. JAMA 2005; 294: 1773-1781. (Pubitemid 41434623)
105. McCarty CA, Wilke RA. Biobanking and pharmacogenetics. Pharmacogenomics 2010; 11: 637-641.
106. Peissig P, Sirohi E, Berg RL, Brown-Switzer C, Ghebranious N, McCarty CA et al. Basic Clin Pharmacol Toxicol 2007; 100: 286-288.
107. Wilke RA, Berg RL, Linneman JG, Zhao C-F, McCarty CA, Krauss RM. Characterization of LDL-cholesterol lowering efficacy for atorvastatin in a population-based DNA biorepository. Basic Clin Pharmacol Toxicol 2008; 103: 354-359.
108. Wilke RA, Reif DM, Moore JH. Combinatorial pharmacogenetics. Nat Rev Drug Discov 2005; 4: 911-918. (Pubitemid 41637693)
109. Wilke RA, Lin D, Roden DM, Watkins PB, Flockhart D, Zineh I et al. Identifying genetic risk factors for serious adverse drug reactions-current progress and challenges. Nat Rev Drug Discov 2007; 6: 904-916. (Pubitemid 350042398)
110. Johnson LW, Weinstock RS. The metabolic syndrome: concepts and controversy. Mayo Clin Proc 2006; 81: 1615-1620. (Pubitemid 44871905)
111. Krauss RM. Insulin resistance syndrome and dyslipidemia. Endocr Pract 2003; 9(Suppl 2): 67-72.
112. Wilke RA, Xu H, Denny JC, Roden DM, Krauss RM, McCarty CA et al. The emerging role of electronic medical records in pharmacoge-nomics. Clin Pharmacol Ther 2010 (in press).