Impact of 3’UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: A pilot study

International Journal of Clinical and Experimental Medicine

Volumn 8, Issue 4, 2015, Pages 5978-5988

  Zambrano, Tomás ^a,b   Hirata, Mario Hiroyuki ^a   Cerda, Álvaro ^a,b   Dorea, Egidio L ^a   Pinto, Gelba A ^a   Gusukuma, Maria C ^a   Bertolami, Marcelo C ^c   Salazar, Luis A ^b   Hirata, Rosario Dominguez Crespo ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b UNIVERSIDAD DE LA FRONTERA   (Chile)

^c NONE

Author keywords

Atorvastatin; Cholesterol; LDLR; MicroRNAs; PCSK9; Polymorphism

Indexed keywords

ATORVASTATIN; LOW DENSITY LIPOPROTEIN RECEPTOR;

3' UNTRANSLATED REGION; ADULT; ARTICLE; DYSLIPIDEMIA; FEMALE; GENE FREQUENCY; GENETIC HETEROGENEITY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; HYPERCHOLESTEROLEMIA; LIPID BLOOD LEVEL; LOW DENSITY LIPOPROTEIN RECEPTOR KO MOUSE; MALE; PCSK9 MOUSE; PILOT STUDY; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84931292072     PISSN: None     EISSN: 19405901     Source Type: Journal    
DOI: None     Document Type: Article

References (48)

1. Welch CL, Xia YR, Shechter I, Farese R, Mehrabian M, Mehdizadeh S, Warden CH and Lusis AJ. Genetic regulation of cholesterol homeostasis: chromosomal organization of candidate genes. J Lipid Res 1996; 37: 1406-1421.
2. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB and Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995; 92: 3172-3177.
3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation 2002; 106: 3143-3421.
4. Blasiole DA, Oler AT and Attie AD. Regulation of ApoB secretion by the low density lipoprotein receptor requires exit from the endoplasmic reticulum and interaction with ApoE or ApoB. J Biol Chem 2008; 283: 11374-11381.
5. Kwon HJ, Lagace TA, McNutt MC, Horton JD and Deisenhofer J. Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A 2008; 105: 1820-1825.
6. Pullinger CR, Hennessy LK, Chatterton JE, Liu W, Love JA, Mendel CM, Frost PH, Malloy MJ, Schumaker VN and Kane JP. Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity. J Clin Invest 1995; 95: 1225-1234.
7. van der Graaf A, Avis HJ, Kusters DM, Vissers MN, Hutten BA, Defesche JC, Huijgen R, Fouchier SW, Wijburg FA, Kastelein JJ and Wiegman A. Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children. Circulation 2011; 123: 1167-1173.
8. Twisk J, Gillian-Daniel DL, Tebon A, Wang L, Barrett PH and Attie AD. The role of the LDL receptor in apolipoprotein B secretion. J Clin Invest 2000; 105: 521-532.
9. Yang KC, Su YN, Shew JY, Yang KY, Tseng WK, Wu CC and Lee YT. LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population. J Formos Med Assoc 2007; 106: 799-807.
10. Salazar LA, Hirata MH, Cavalli SA, Nakandakare ER, Forti N, Diament J, Giannini SD, Bertolami MC and Hirata RD. Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations. Hum Mutat 2002; 19: 462-463.
11. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG and Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003; 34: 154-156.
12. Abifadel M, Rabes JP, Devillers M, Munnich A, Erlich D, Junien C, Varret M and Boileau C. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat 2009; 30: 520-529.
13. Law MR, Wald NJ and Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003; 326: 1423.
14. Guo S, Wang R, Yang Z, Li K and Wang Q. Effects of atorvastatin on serum lipids, serum inflammation and plaque morphology in patients with stable atherosclerotic plaques. Exp Ther Med 2012; 4: 1069-1074.
15. Albert MA, Staggers J, Chew P and Ridker PM. The pravastatin inflammation CRP evaluation (PRINCE): rationale and design. Am Heart J 2001; 141: 893-898.
16. Liao JK. Isoprenoids as mediators of the biological effects of statins. J Clin Invest 2002; 110: 285-288.
17. Takemoto M and Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 1712-1719.
18. Pocathikorn A, Taylor RR and Mamotte CD. Atorvastatin increases expression of low-density lipoprotein receptor mRNA in human circulating mononuclear cells. Clin Exp Pharmacol Physiol 2010; 37: 471-476.
19. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, Bernier L and Prat A. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2004; 24: 1454-1459.
20. Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G and 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.
21. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK and Tomaselli GF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129: S1-45.
22. Chahoud G, Aude YW and Mehta JL. Dietary recommendations in the prevention and treatment of coronary heart disease: do we have the ideal diet yet? Am J Cardiol 2004; 94: 1260-1267.
23. Friedewald WT, Levy RI and Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502.
24. Salazar LA, Hirata MH, Cavalli SA, Machado MO and Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998; 44: 1748-1750.
25. Cross DS, Ivacic LC, Stefanski EL and McCarty CA. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project. BMC Genet 2010; 11: 51.
26. Alex L, Chahil JK, Lye SH, Bagali P and Ler LW. Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population. J Hum Genet 2012; 57: 358-362.
27. Handley LJ, Manica A, Goudet J and Balloux F. Going the distance: human population genetics in a clinal world. Trends Genet 2007; 23: 432-439.
28. Silbiger VN, Hirata MH, Luchessi AD, Genvigir FD, Cerda A, Rodrigues AC, Willrich MA, Arazi SS, Dorea EL, Bernik MM, Faludi AA, Bertolami MC, Santos C, Carracedo A, Salas A, Freire A, Lareu MV, Phillips C, Porras-Hurtado L, Fondevila M and Hirata RD. Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population. Genet Test Mol Biomarkers 2012; 16: 524-530.
29. Alves-Silva J, da Silva Santos M, Guimaraes PE, Ferreira AC, Bandelt HJ, Pena SD and Prado VF. The ancestry of Brazilian mtDNA lineages. Am J Hum Genet 2000; 67: 444-461.
30. Pena SD, Bastos-Rodrigues L, Pimenta JR and Bydlowski SP. DNA tests probe the genomic ancestry of Brazilians. Braz J Med Biol Res 2009; 42: 870-876.
31. Garcia-Martin E, Martinez C, Ladero JM and Agundez JA. Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. Mol Diagn Ther 2006; 10: 29-40.
32. Chen W, Wang S, Ma Y, Zhou Y, Liu H, Strnad P, Kraemer FB, Krauss RM and Liu J. Analysis of polymorphisms in the 3’ untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response. Int J Mol Med 2008; 21: 345-353.
33. van Zyl T, Jerling JC, Conradie KR and Feskens EJ. Common and rare single nucleotide polymorphisms in the LDLR gene are present in a black South African population and associate with low-density lipoprotein cholesterol levels. J Hum Genet 2014; 59: 88-94.
34. Petersen DC, Libiger O, Tindall EA, Hardie RA, Hannick LI, Glashoff RH, Mukerji M, Fernandez P, Haacke W, Schork NJ and Hayes VM. Complex patterns of genomic admixture within southern Africa. PLoS Genet 2013; 9: e1003309.
35. Pena SD, Di Pietro G, Fuchshuber-Moraes M, Genro JP, Hutz MH, Kehdy Fde S, Kohlrausch F, Magno LA, Montenegro RC, Moraes MO, de Moraes ME, de Moraes MR, Ojopi EB, Perini JA, Racciopi C, Ribeiro-Dos-Santos AK, Rios-Santos F, Romano-Silva MA, Sortica VA and Suarez-Kurtz G. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS One 2011; 6: e17063.
36. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA and Horton JD. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A 2005; 102: 5374-5379.
37. Graham MJ, Lemonidis KM, Whipple CP, Subramaniam A, Monia BP, Crooke ST and Crooke RM. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 2007; 48: 763-767.
38. Chan JC, Piper DE, Cao Q, Liu D, King C, Wang W, Tang J, Liu Q, Higbee J, Xia Z, Di Y, Shetterly S, Arimura Z, Salomonis H, Romanow WG, Thibault ST, Zhang R, Cao P, Yang XP, Yu T, Lu M, Retter MW, Kwon G, Henne K, Pan O, Tsai MM, Fuchslocher B, Yang E, Zhou L, Lee KJ, Daris M, Sheng J, Wang Y, Shen WD, Yeh WC, Emery M, Walker NP, Shan B, Schwarz M and Jackson SM. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci U S A 2009; 106: 9820-9825.
39. Choi S, Aljakna A, Srivastava U, Peterson BR, Deng B, Prat A and Korstanje R. Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of serum in mice lacking Pcsk9. Lipids Health Dis 2013; 12: 112.
40. Bushati N and Cohen SM. microRNA functions. Annu Rev Cell Dev Biol 2007; 23: 175-205.
41. Doench JG and Sharp PA. Specificity of microRNA target selection in translational repression. Genes Dev 2004; 18: 504-511.
42. Ryan BM, Robles AI and Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 2010; 10: 389-402.
43. Maragkakis M, Alexiou P, Papadopoulos GL, Reczko M, Dalamagas T, Giannopoulos G, Goumas G, Koukis E, Kourtis K, Simossis VA, Sethupathy P, Vergoulis T, Koziris N, Sellis T, Tsanakas P and Hatzigeorgiou AG. Accurate microRNA target prediction correlates with protein repression levels. BMC Bioinformatics 2009; 10: 295.
44. Careskey HE, Davis RA, Alborn WE, Troutt JS, Cao G and Konrad RJ. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008; 49: 394-398.
45. Brown MS and Goldstein JL. Biomedicine. Lowering LDL--not only how low, but how long? Science 2006; 311: 1721-1723.
46. Wilson PW. High-density lipoprotein, low-density lipoprotein and coronary artery disease. Am J Cardiol 1990; 66: 7A-10A.
47. Anderson JM, Cerda A, Hirata MH, Rodrigues AC, Dorea EL, Bernik MM, Bertolami MC, Faludi AA and Hirata RD. Influence of PCSK9 polymorphisms on plasma lipids and response to atorvastatin treatment in Brazilian subjects. J Clin Lipidol 2014; 8: 256-264.
48. Simon JA, Lin F, Hulley SB, Blanche PJ, Waters D, Shiboski S, Rotter JI, Nickerson DA, Yang H, Saad M and Krauss RM. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study. Am J Cardiol 2006; 97: 843-850.