Genetic Determinants of Inter-Individual Variability in Statin Therapy
DOI:
https://doi.org/10.12775/QS.2026.53.69507Keywords
Pharmacogenomics, statins, pharmacodynamics, genetic polymorphismsAbstract
Statins, or HMG-CoA reductase inhibitors, represent one of the most extensively researched and frequently prescribed pharmacological agents, primarily utilized to reduce cardiovascular risk through the modulation of serum cholesterol levels. Although their efficacy in reducing global mortality and cardiovascular events is well-established, genetic variability persists among different populations which may predispose patients to dose-related adverse effects and reduced efficancy of statin therapy. This heterogeneity has driven a shift in the scientific landscape toward exploring common genetic polymorphisms within the genes encoding genes involved in pharmacodynamic pathways. This review aims to provide a comprehensive analysis of clinically significant polymorphisms within the pharmacodynamic pathways of statins.
Methods: A systematic literature review was conducted in accordance with PRISMA guidelines. Databases including PubMed, Embase, and the Cochrane Library were searched for peer-reviewed publications from 2021 to 2025. Following a rigorous selection process based on Evidence-Based Medicine (EBM) criteria.
Conclusions: Despite rapid progress in the field of pharmacogenomics, the role of genetic polymorphisms among genes involved in pharmacodynamic pathways of statin therapy still requires more research in order to establish robust evidence of their role in the overall lipid-lowering efficacy of statins.
References
1. Röhrl C, Stangl H. Cholesterol metabolism—physiological regulation and pathophysiological deregulation by the endoplasmic reticulum. Wiener Medizinische Wochenschrift. 2018;168(11-12). doi:10.1007/s10354-018-0626-2
2. Egom EE, Rose RA, Neyses L, Soran H, Cleland JGF, Mamas MA. Activation of sphingosine-1-phosphate signalling as a potential underlying mechanism of the pleiotropic effects of statin therapy. Crit Rev Clin Lab Sci. 2013;50(3). doi:10.3109/10408363.2013.813013
3. Zheng E, Warchoł I, Mejza M, et al. Exploring Anti-Inflammatory Treatment as Upstream Therapy in the Management of Atrial Fibrillation. J Clin Med. 2025;14(3). doi:10.3390/jcm14030882
4. Marais AD. Apolipoprotein E and Atherosclerosis. Curr Atheroscler Rep. 2021;23(7). doi:10.1007/s11883-021-00933-4
5. Zhang L, He S, Li Z, et al. Apolipoprotein e polymorphisms contribute to statin response in Chinese ASCVD patients with dyslipidemia. Lipids Health Dis. 2019;18(1). doi:10.1186/s12944-019-1069-5
6. Bi QQ, Zhou XY, Lu YQ, et al. Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke. Front Cardiovasc Med. 2022;9. doi:10.3389/fcvm.2022.1024014
7. Weisgraber KH. Apolipoprotein E distribution among human plasma lipoproteins: Role of the cysteine-arginine interchange at residue 112. J Lipid Res. 1990;31(8). doi:10.1016/s0022-2275(20)42621-5
8. Wang S, Li B, Solomon V, et al. Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4. Mol Neurodegener. 2022;17(1). doi:10.1186/s13024-022-00549-5
9. Corson MA. Phospholipase A2 inhibitors in atherosclerosis: the race is on. The Lancet. 2009;373(9664). doi:10.1016/S0140-6736(09)60378-0
10. Zintzaras E, Kitsios GD, Triposkiadis F, Lau J, Raman G. APOE gene polymorphisms and response to statin therapy. Pharmacogenomics Journal. 2009;9(4). doi:10.1038/tpj.2009.25
11. Sniderman AD, Thanassoulis G, Glavinovic T, et al. Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review. JAMA Cardiol. 2019;4(12). doi:10.1001/jamacardio.2019.3780
12. Yusuf PS, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet. 2004;364(9438). doi:10.1016/S0140-6736(04)17018-9
13. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): A prospective study. Lancet. 2001;358(9298). doi:10.1016/S0140-6736(01)07098-2
14. Walldius G, Aastveit AH, Jungner I. Stroke mortality and the apoB/apoA-I ratio: Results of the AMORIS prospective study. J Intern Med. 2006;259(3). doi:10.1111/j.1365-2796.2005.01610.x
15. Niu C, Luo Z, Yu L, et al. Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: A meta-analysis. Lipids Health Dis. 2017;16(1). doi:10.1186/s12944-017-0558-7
16. Zafar M, Mirza MR, Awan FR, et al. Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-02211-4
17. Vimaleswaran KS, Minihane AM, Li Y, et al. The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults. Nutr Metab (Lond). 2015;12(1). doi:10.1186/s12986-015-0002-9
18. Gu QL, Han Y, Lan YM, et al. Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population. Brazilian Journal of Medical and Biological Research. 2017;50(11). doi:10.1590/1414-431x20176613
19. Ye P, Shang Y, Ding X. The influence of apolipoprotein B and E gene polymorphisms on the response to simvastatin therapy in patients with hyperlipidemia. Chinese Medical Sciences Journal. 2003;18(1).
20. Abdulfattah SY, Al-Awadi SJ. ApoB gene polymorphism (rs676210) and its pharmacogenetics impact on atorvastatin response among Iraqi population with coronary artery disease. Journal of Genetic Engineering and Biotechnology. 2021;19(1). doi:10.1186/s43141-021-00193-4
21. Nikolajevic Starcevic J, Santl Letonja M, Praznikar ZJ, Makuc J, Vujkovac AC, Petrovic D. Polymorphisms XbaI (rs693) and EcoRI (rs1042031) of the ApoB gene are associated with carotid plaques but not with carotid intima-media thickness in patients with diabetes mellitus type 2. Vasa. 2014;43(3). doi:10.1024/0301-1526/a000346
22. De Grooth GJ, Zerba KE, Huang SP, et al. The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: No interaction with the response to pravastatin therapy and no effects on cardiovascular outcome - A prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy. J Am Coll Cardiol. 2004;43(5). doi:10.1016/j.jacc.2003.08.056
23. Lu Y, Tayebi N, Li H, Saha N, Yang H, Heng CK. Association of CETP Taq1B and -629C > A polymorphisms with coronary artery disease and lipid levels in the multi-ethnic Singaporean population. Lipids Health Dis. 2013;12(1). doi:10.1186/1476-511X-12-85
24. Maitland-van der Zee AH, Klungel OH, Stricker BHC, et al. Genetic polymorphisms: Importance for response to HMG-CoA reductase inhibitors. Atherosclerosis. 2002;163(2). doi:10.1016/S0021-9150(01)00725-0
25. Montali A, McMahon AD, Zwinderman AH, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111(3).
26. Eleni B, Vana K, Maria B, Anastasia T, Despoina P, Genovefa K. The Cholesteryl Ester Transfer Protein (CETP) Taqib and I405V Gene Polymorphisms and Statin Treatment. J Pharmacogenomics Pharmacoproteomics. 2017;08(01). doi:10.4172/2153-0645.1000168
27. Gu GL, Xu XL, Yang QY, Zeng RL. Effect of CETP polymorphism on atorvastatin lipid-regulating effect and clinical prognosis of patients with coronary heart disease. Medical Science Monitor. 2014;20. doi:10.12659/MSM.892711
28. Blankenberg S, Rupprecht HJ, Bickel C, et al. Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary artery disease. J Am Coll Cardiol. 2003;41(11). doi:10.1016/S0735-1097(03)00408-X
29. Anagnostopoulou K, Kolovou G, Kostakou P, Mihas C, Mikhailidis D, Cokkinos D V. Pharmacogenetic study of cholesteryl ester transfer protein gene and simvastatin treatment in hypercholesterolaemic subjects. Expert Opin Pharmacother. 2007;8(15). doi:10.1517/14656566.8.15.2459
30. Kolovou G, Mihas C, Anagnostopoulou K, et al. Cholesteryl Ester Transfer Protein Gene and Effectiveness of Lipid Lowering of Atorvastatin. Open Cardiovasc Med J. 2015;4(1). doi:10.2174/1874192401004010297
31. Meiner V, Friedlander Y, Milo H, et al. Cholesteryl ester transfer protein (CETP) genetic variation and early onset of non-fatal myocardial infarction. Ann Hum Genet. 2008;72(6). doi:10.1111/j.1469-1809.2008.00464.x
32. Goodarzynejad H, Boroumand M, Behmanesh M, Ziaee S, Jalali A. Cholesteryl ester transfer protein gene polymorphism (I405V) and premature coronary artery disease in an Iranian population. Bosn J Basic Med Sci. Published online 2016. doi:10.17305/bjbms.2016.942
33. Lythgoe C, Perkes A, Peterson M, et al. Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study. Neurobiol Aging. 2015;36(1). doi:10.1016/j.neurobiolaging.2014.08.022
34. Sahmani M, Ghaleh TD, Darabi M, Darabi M, Rashvand Z, Najafipour R. I405V polymorphism of CETP gene and lipid profile in women with endometriosis. Gynecological Endocrinology. 2013;29(7). doi:10.3109/09513590.2013.797396
35. Srisawasdi P, Rodcharoen P, Vanavanan S, et al. Association of CETP gene variants with atherogenic dyslipidemia among thai patients treated with statin. Pharmgenomics Pers Med. 2021;14. doi:10.2147/PGPM.S278671
36. De Keyser CE, Eijgelsheim M, Hofman A, et al. Single nucleotide polymorphisms in genes that are associated with a modified response to statin therapy: The Rotterdam Study. Pharmacogenomics Journal. 2011;11(1). doi:10.1038/tpj.2010.11
37. Guo S, Hu Y, Ding Y, et al. Association between eight functional polymorphisms and haplotypes in the cholesterol ester transfer protein (CETP) gene and dyslipidemia in national minority adults in the far west region of China. Int J Environ Res Public Health. 2015;12(12). doi:10.3390/ijerph121215036
38. Zhao X, Li J, Tang X, et al. Association of NPC1L1 and HMGCR Gene Polymorphisms with Major Adverse Cardiac and Cerebrovascular Events in Patients with Three-Vessel Disease. Hum Gene Ther. 2021;32(11-12). doi:10.1089/hum.2020.229
39. Freitas RN, Khaw KT, Wu K, et al. HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study. European Journal of Cardiovascular Prevention & Rehabilitation. 2010;17(1):89-93. doi:10.1097/HJR.0b013e328330be77
40. Ma S, Sun W, Gao L, Liu S. Therapeutic targets of hypercholesterolemia: HMGCR and LDLR. Diabetes, Metabolic Syndrome and Obesity. 2019;12. doi:10.2147/DMSO.S219013
41. Guan ZW, Wu KR, Li R, et al. Pharmacogenetics of statins treatment: Efficacy and safety. J Clin Pharm Ther. 2019;44(6). doi:10.1111/jcpt.13025
42. Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or Both: A 2 × 2 factorial mendelian randomization study. J Am Coll Cardiol. 2015;65(15). doi:10.1016/j.jacc.2015.02.020
43. Poduri A, Khullar M, Bahl A, Sehrawat BS, Sharma Y, Talwar KK. Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy. DNA Cell Biol. 2010;29(10). doi:10.1089/dna.2009.1008
44. Zhao X, Xu J, Tang X, et al. Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease. Front Cardiovasc Med. 2021;8. doi:10.3389/fcvm.2021.704501
45. Medina MW, Krauss RM. The Role of HMGCR Alternative Splicing in Statin Efficacy. Trends Cardiovasc Med. 2009;19(5). doi:10.1016/j.tcm.2009.10.003
46. Chen YC, Chen YDI, Li X, et al. The HMG-CoA Reductase gene and lipid and lipoprotein levels: The multi-ethnic study of atherosclerosis. Lipids. 2009;44(8). doi:10.1007/s11745-009-3314-6
47. Cuevas A, Fernández C, Ferrada L, et al. HMGCR rs17671591 SNP Determines Lower Plasma LDL-C after Atorvastatin Therapy in Chilean Individuals. Basic Clin Pharmacol Toxicol. 2016;118(4). doi:10.1111/bcpt.12493
48. Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004;291(23). doi:10.1001/jama.291.23.2821
49. Chien KL, Wang KC, Chen YC, et al. Common sequence variants in pharmacodynamic and pharmacokinetic pathway-related genes conferring LDL cholesterol response to statins. Pharmacogenomics. 2010;11(3). doi:10.2217/pgs.09.160
50. Leitersdorf E, Eisenberg S, Eliav O, et al. Genetic determinants of responsiveness to the HMG-CoA reductase inhibitor fluvastatin in patients with molecularly defined heterozygous familial hypercholesterolemia. Circulation. 1993;87(4 SUPPL.).
51. Jeenah M, September W, Graadt van Roggen F, de Villiers W, Seftel H, Marais D. Influence of specific mutations at the LDL-receptor gene locus on the response to simvastatin therapy in Afrikaner patients with heterozygous familial hypercholesterolaemia. Atherosclerosis. 1993;98(1). doi:10.1016/0021-9150(93)90222-G
52. Kajinami K, Yagi K, Higashikata T, Inazu A, Koizumi J, Mabuchi H. Low-density lipoprotein receptor genotype-dependent response to cholesterol lowering by combined pravastatin and cholestyramine in familial hypercholesterolemia. American Journal of Cardiology. 1998;82(1). doi:10.1016/S0002-9149(98)00230-6
53. Couture P, Brun LD, Szots F, et al. Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1998;18(6). doi:10.1161/01.ATV.18.6.1007
54. Santos PCJL, Morgan AC, Jannes CE, et al. Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2014;233(1). doi:10.1016/j.atherosclerosis.2013.12.028
55. Perez De Isla L, Alonso R, Watts GF, et al. Attainment of LDL-cholesterol treatment goals in patients with familial hypercholesterolemia: 5-year SAFEHEART registry follow-up. J Am Coll Cardiol. 2016;67(11). doi:10.1016/j.jacc.2016.01.008
56. Chasman DI, Giulianini F, MacFadyen J, Barratt BJ, Nyberg F, Ridker PM. Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: The justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin (JUPITER) trial. Circ Cardiovasc Genet. 2012;5(2). doi:10.1161/CIRCGENETICS.111.961144
57. Zhu H, Tucker HM, Grear KE, et al. A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol. Hum Mol Genet. 2007;16(14). doi:10.1093/hmg/ddm124
58. Polisecki E, Muallem H, Maeda N, et al. Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. Atherosclerosis. 2008;200(1). doi:10.1016/j.atherosclerosis.2007.12.004
59. Abdulfattah SY, Abdullah SJ, Alsaffar HB. A Study to Explore the LDLR Gene Polymorphisms Contribute to Atorvastatin Response in a Sample of Iraqi Population with Atherosclerotic Coronary Artery Disease. Karbala International Journal of Modern Science. 2020;6(1). doi:10.33640/2405-609X.1361
60. Mangravite LM, Medina MW, Cui J, et al. Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin. Arterioscler Thromb Vasc Biol. 2010;30(7). doi:10.1161/ATVBAHA.110.203273
61. Fiegenbaum M, Silveira FR, Van der Sand CR, et al. Determinants of variable response to simvastatin treatment: The role of common variants of SCAP, SREBF-1a and SREBF-2 genes. Pharmacogenomics Journal. 2005;5(6). doi:10.1038/sj.tpj.6500334
62. Salek L, Lutucuta S, Ballantyne CM, Gotto AM, Marian A. Effects of SREBF-1a and SCAP polymorphisms on plasma levels of lipids, severity, progression and regression of coronary atherosclerosis and response to therapy with fluvastatin. J Mol Med (Berl). 2002;80(11). doi:10.1007/s00109-002-0381-z
63. Abifadel M, Varret M, Rabès JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2). doi:10.1038/ng1161
64. Taylor BA, Thompson PD. Statins and Their Effect on PCSK9—Impact and Clinical Relevance. Curr Atheroscler Rep. 2016;18(8). doi:10.1007/s11883-016-0604-3
65. Nozue T. Lipid lowering therapy and circulating PCSK9 concentration. J Atheroscler Thromb. 2017;24(9). doi:10.5551/jat.RV17012
66. De Keyser CE, Becker ML, Hofman A, et al. The rs13064411 polymorphism in the WDR52 gene, associated with PCSK9 levels, modifies statin-induced changes in serum total and LDL cholesterol levels. Pharmacogenet Genomics. 2015;25(3). doi:10.1097/FPC.0000000000000120
67. Feng Q, Wei WQ, Chung CP, et al. The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy. Pharmacogenomics Journal. 2017;17(2). doi:10.1038/tpj.2016.3
68. Zambrano T, Caamaño JM, Rosales A, Saavedra N, Lanas F, Salazar LA. PCSK9 polymorphism rs505151 affects lipid-lowering response to atorvastatin but does not influence ezetimibe therapy in Chilean subjects. CORONARY ARTERY DISEASE: 2011 UPDATE: FROM PREVENTION TO INTERVENTION. 2011;(9th International Congress on Coronary Artery Disease (ICCAD)).
69. Santoso A, Yulianto Y, Simarmata H, Putra AN, Listiyaningsih E. Effect of PCSK9 E670G and R46L Polymorphisms on Major Adverse Cardio-Cerebrovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. International Journal of Angiology. 2021;30(1). doi:10.1055/s-0041-1722875
70. Chen SN, Ballantyne CM, Gotto AM, Tan Y, Willerson JT, Marian AJ. A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis. J Am Coll Cardiol. 2005;45(10). doi:10.1016/j.jacc.2005.01.051
71. Rojas C, Ramírez H, Salazar LA, Kalergis AM, Gálvez AS, Escobar-Vera J. Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels. J Clin Lab Anal. 2019;33(9). doi:10.1002/jcla.23001
72. Rashid S, Curtis DE, Garuti R, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A. 2005;102(15). doi:10.1073/pnas.0501652102
73. Wanmasae S, Sirintronsopon W, Porntadavity S, Jeenduang N. The effect of APOE , CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients. Cardiovasc Ther. 2017;35(6). doi:10.1111/1755-5922.12302
74. Scartezini M, Hubbart C, Whittall RA, Cooper JA, Neil AHW, Humphries SE. The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men. Clin Sci. 2007;113(11-12). doi:10.1042/CS20070150
75. Polisecki E, Peter I, Robertson M, et al. Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population. Atherosclerosis. 2008;200(1). doi:10.1016/j.atherosclerosis.2007.12.005
76. Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40(2). doi:10.1038/ng.75
77. Castillo-Avila RG, González-Castro TB, Tovilla-Zárate CA, et al. Association between Genetic Variants of CELSR2-PSRC1-SORT1 and Cardiovascular Diseases: A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis. 2023;10(3). doi:10.3390/jcdd10030091
78. Tan J, Che Y, Liu Y, et al. CELSR2 deficiency suppresses lipid accumulation in hepatocyte by impairing the UPR and elevating ROS level. FASEB Journal. 2021;35(10). doi:10.1096/fj.202100786RR
79. Andersen JL, Schrøder TJ, Christensen S, et al. Identification of the first small-molecule ligand of the neuronal receptor sortilin and structure determination of the receptor-ligand complex. Acta Crystallogr D Biol Crystallogr. 2014;70(2). doi:10.1107/S1399004713030149
80. Patel KM, Strong A, Tohyama J, et al. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res. 2015;116(5). doi:10.1161/CIRCRESAHA.116.305811
81. Kjolby M, Nielsen MS, Petersen CM. Sortilin, Encoded by the Cardiovascular Risk Gene SORT1, and Its Suggested Functions in Cardiovascular Disease. Curr Atheroscler Rep. 2015;17(4). doi:10.1007/s11883-015-0496-7
82. Gustafsen C, Kjolby M, Nyegaard M, et al. The hypercholesterolemia-risk gene SORT1 facilitates PCSK9 secretion. Cell Metab. 2014;19(2). doi:10.1016/j.cmet.2013.12.006
83. Chai T, Wang Z, Yang X, Qiu Z, Chen L. PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels. Front Cardiovasc Med. 2022;9. doi:10.3389/fcvm.2022.763015
84. Kleber ME, Renner W, Grammer TB, et al. Association of the single nucleotide polymorphism rs599839 in the vicinity of the sortilin 1 gene with LDL and triglyceride metabolism, coronary heart disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health Study. Atherosclerosis. 2010;209(2). doi:10.1016/j.atherosclerosis.2009.09.068
85. Goettsch C, Kjolby M, Aikawa E. Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases. Arterioscler Thromb Vasc Biol. 2018;38(1). doi:10.1161/ATVBAHA.117.310292
86. Hubácek JA, Adámková V, Lánská V, et al. Variant within CELSR2/PSRC1/SORT1, but not within CILP2/PBX4, PCSK9 and APOB genes, has a potential to influence statin treatment efficacy. J Appl Biomed. 2012;10(1). doi:10.2478/v10136-012-0001-3
87. Hopewell JC, Parish S, Offer A, et al. Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study. Eur Heart J. 2013;34(13). doi:10.1093/eurheartj/ehs344
88. Postmus I, Trompet S, Deshmukh HA, et al. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat Commun. 2014;5. doi:10.1038/ncomms6068
89. Deshmukh HA, Colhoun HM, Johnson T, et al. Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: Importance of Lp(a). J Lipid Res. 2012;53(5). doi:10.1194/jlr.P021113
90. Banach M, Aronow WS, Serban MC, Rysz J, Voroneanu L, Covic A. Lipids, blood pressure and kidney update 2015. Lipids Health Dis. 2015;14(1). doi:10.1186/s12944-015-0169-0
91. Hunninghake DB, Stein EA, Mellies MJ. Effects of One Year of Treatment with Pravastatin, an HMG‐CoA Reductase Inhibitor, on Lipoprotein a. The Journal of Clinical Pharmacology. 1993;33(6). doi:10.1002/j.1552-4604.1993.tb04706.x
92. Zhu L, Fang Y, Gao B, et al. Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease. BMC Cardiovasc Disord. 2022;22(1). doi:10.1186/s12872-022-02932-y
93. Mega JL, Stitziel NO, Smith JG, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: An analysis of primary and secondary prevention trials. The Lancet. 2015;385(9984). doi:10.1016/S0140-6736(14)61730-X
94. Wei WQ, Li X, Feng Q, et al. LPA variants are associated with residual cardiovascular risk in patients receiving statins. Circulation. 2018;138(17). doi:10.1161/CIRCULATIONAHA.117.031356
95. Santos PCJL, Bueno CT, Lemos PA, Krieger JE, Pereira AC. LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography. Lipids Health Dis. 2014;13(1). doi:10.1186/1476-511X-13-74
96. Clarke R, Peden JF, Hopewell JC, et al. Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease. New England Journal of Medicine. 2009;361(26). doi:10.1056/nejmoa0902604
97. H.A. D, H.M. C, T. J, et al. Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: Importance of Lp(a). J Lipid Res. 2012;53(5).
98. Knack RS, Grinberg H, Knack RS, Knack RES, Sá KMM, Hanada TZB. The impact of SNP rs3798220 on the LPA gene in atherosclerotic disease. Atherosclerosis. 2022;355. doi:10.1016/j.atherosclerosis.2022.06.400
99. Li ZG, Li G, Zhou YL, et al. Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention. Lipids Health Dis. 2013;12(1). doi:10.1186/1476-511X-12-127
100. Kronenberg F. Human Genetics and the Causal Role of Lipoprotein(a) for Various Diseases. Cardiovasc Drugs Ther. 2016;30(1). doi:10.1007/s10557-016-6648-3
101. Schachtl-Riess JF, Kheirkhah A, Grüneis R, et al. Frequent LPA KIV-2 Variants Lower Lipoprotein(a) Concentrations and Protect Against Coronary Artery Disease. J Am Coll Cardiol. 2021;78(5). doi:10.1016/j.jacc.2021.05.037
102. Melhem AL, Chourasia MK, Bigossi M, et al. Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records. Front Genet. 2021;12. doi:10.3389/fgene.2021.713181
103. Vanwong N, Tipnoppanon S, Na Nakorn C, et al. Association of Drug-Metabolizing Enzyme and Transporter Gene Polymorphisms and Lipid-Lowering Response to Statins in Thai Patients with Dyslipidemia. Pharmgenomics Pers Med. 2022;15. doi:10.2147/PGPM.S346093
104. Santos LEG, Nevado JB, Cutiongco-De la Paz EMC, et al. Variants Near CETP, MTTP and BUD13-ZPR1-APOA5 may be Nominally Associated with Poor Statin Response among Filipinos. Acta Med Philipp. 2022;56(10). doi:10.47895/amp.vi0.2353
105. Ruiz-Iruela C, Padró-Miquel A, Pintó-Sala X, et al. KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment. PLoS One. 2018;13(10). doi:10.1371/journal.pone.0205430
106. Kajinami K, Brousseau ME, Ordovas JM, Schaefer EJ. Interactions between common genetic polymorphisms in ABCG5/G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin. Atherosclerosis. 2004;175(2). doi:10.1016/j.atherosclerosis.2004.03.015
107. Polisecki E, Peter I, Simon JS, et al. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly. J Lipid Res. 2010;51(5). doi:10.1194/jlr.P001172
108. Chan DC, Watts GF, Wang J, Hegele RA, Van Bockxmeer FM, Barrett PHR. Variation in Niemann-Pick C1-like 1 gene as a determinant of apolipoprotein B-100 kinetics and response to statin therapy in centrally obese men. Clin Endocrinol (Oxf). 2008;69(1). doi:10.1111/j.1365-2265.2007.03144.x
109. Hu M, Lui SSH, Tam LS, Li EK, Tomlinson B. The farnesoid X receptor -1G>T polymorphism influences the lipid response to rosuvastatin. J Lipid Res. 2012;53(7):1384-1389. doi:10.1194/jlr.M026054
110. Zheng E, Madura P, Grandos J, et al. When the same treatment has different response: The role of pharmacogenomics in statin therapy. Biomedicine & Pharmacotherapy. 2024;170:115966. doi:10.1016/j.biopha.2023.115966
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Copyright (c) 2026 Agnieszka Olejnik, Edward Zheng, Maria Możdżan, Laura Biskup, Beata Huszcza, Konrad Gronek, Julia Kaczmarek, Jakub Grandos, Dominik Gajewski, Zuzanna Głowacka, Kinga Kościołek
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