No association between LDL receptor and CETP genetic variants and atorvastatin response in Jordanian hyperlipidemic patients
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Malek Zihlif
,
Suhad Otoum
Abstract
Objectives
Atorvastatin is commonly used medication to achieve low levels of low-density lipoproteins (LDL). Cholesteryl ester transfer protein (CETP) and LDL receptor (LDLR) genetic variants can affect the cholesterol transport and hence may affect on atorvastatin response. This study aimed to investigate the influence of LDLR AvaII, CETP TaqIb, and Rs1532624 on the efficacy of 20 mg atorvastatin among Jordanian hyperlipidemic patients.
Methods
One hundred and 50 blood samples were collected from hyperlipidemic patients in the University of Jordan Hospital. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of LDLR AvaII and CETP TaqIb genetic variants. The genotyping of CETP Rs1532624 variant was done by Sanger DNA-Sequencing.
Results
LDLR AvaII and CETP TaqIb and Rs1532624 variants showed a significant (p value < 0.05) association with the baseline of the LDL at the time of diagnoses. On the other hand, none of the tested genetic variants showed a significant (p value>0.05) association with LDL reduction after atorvastatin therapy.
Conclusions
Results demonstrated a significant association between the LDLR AvaII and CETP TaqIb, and Rs1532624 genetic variants with the LDL baseline level. However, the atorvastatin therapy among hyperlipidemic patients of Jordanian origin was not affected by any of the tested variants.
Funding source: The University of Jordan
Award Identifier / Grant number: Unassigned
Acknowledgments
The authors would like to acknowledge The Deanship of Graduate Studies, The University of Jordan, for supporting this research.
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Research funding: This work has been funded by The Deanship of Graduate Studies, The University of Jordan.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The protocol of this study was approved by the Institutional Review Board of The University of Jordan Hospital (with reference number 67/2020/8024).
References
1. Maitland-van der Zee, AH, Klungel, OH, Stricker, BH, Monique Verschuren, WM, Kastelein, JJ, Leufkens, HG, et al.. Genetic polymorphisms: importance for response to HMG-CoA reductase inhibitors. Atherosclerosis 2002;163:213–22.10.1016/S0021-9150(01)00725-0Suche in Google Scholar PubMed
2. Mangravite, LM, Thorn, CF, Krauss, RM. Clinical implications of pharmacogenomics of statin treatment. Pharmacogenomics J 2006;6:360–74.10.1038/sj.tpj.6500384Suche in Google Scholar PubMed
3. Freitas, RN, Khaw, KT, Wu, K, Bowman, R, Jeffery, H, Luben, R, et al.. A single nucleotide polymorphism in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene ( HMGCR) influences the serum triacylglycerol relationship with dietary fat and fibre in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study. Br J Nutr 2010;104:765–72.10.1017/S0007114510001145Suche in Google Scholar PubMed
4. Alhawari, H, Jarrar, Y, AlKhatib, MA, Alhawari, H, Momani, M, Zayed, A, et al.. The association of 3-hydroxy-3-methylglutaryl-CoA reductase, Apolipoprotein E, and solute carrier organic anion genetic variants with Atorvastatin response among Jordanian patients with Type 2 diabetes. Life (Basel) 2020;10:232.10.3390/life10100232Suche in Google Scholar PubMed PubMed Central
5. Abdullah, S, Jarrar, Y, Alhawari, H, Abed, E, Zihlif, M. The influence of Endothelial Nitric Oxide Synthase (eNOS) genetic polymorphisms on cholesterol blood levels among Type 2 diabetic patients on Atorvastatin Therapy. Endocr Metab Immune Disord Drug Targets 2021;21:352–9.10.2174/1871530320666200621174858Suche in Google Scholar
6. Abed, E, Jarrar, Y, Alhawari, H, Abdullah, S, Zihlif, M. How the cytochrome 7a1 (CYP7A1) and ATP-binding cassette G8 (ABCG8) genetic variants affect atorvastatin response among type 2 diabetic patients attending the University of Jordan Hospital. Int J Clin Pharm Ther 2021;59:99–108.10.5414/CP203779Suche in Google Scholar PubMed
7. Postmus, I, Verschuren, JJ, de Craen, AJ, Slagboom, PE, Westendorp, RG, Jukema, JW, et al.. Pharmacogenetics of statins: achievements, whole-genome analyses and future perspectives. Pharmacogenomics 2012;13:831–40.10.2217/pgs.12.25Suche in Google Scholar PubMed
8. Barter, P, Rye, KA. Cholesteryl ester transfer protein: its role in plasma lipid transport. Clin Exp Pharmacol Physiol 1994;21:663–72.10.1111/j.1440-1681.1994.tb02569.xSuche in Google Scholar PubMed
9. Kleber, ME, Grammer, TB, Marz, W. High-density lipoprotein (HDL) and cholesteryl ester transfer protein (CETP): role in lipid metabolism and clinical meaning. MMW - Fortschritte Med 2010;152(2 Suppl):47–55.Suche in Google Scholar
10. Maitland-van der Zee, AH, Boerwinkle, E. Pharmacogenetics of response to statins: where do we stand? Curr Atherosclerosis Rep 2005;7:204–8.10.1007/s11883-005-0007-3Suche in Google Scholar PubMed
11. Frisdal, E, Klerkx, AH, Le Goff, W, Tanck, MW, Lagarde, JP, Jukema, JW, et al.. Functional interaction between -629C/A, -971G/A and -1337C/T polymorphisms in the CETP gene is a major determinant of promoter activity and plasma CETP concentration in the REGRESS Study. Hum Mol Genet 2005;14:2607–18.10.1093/hmg/ddi291Suche in Google Scholar PubMed
12. Lu, H, Inazu, A, Moriyama, Y, Higashikata, T, Kawashiri, MA, Yu, W, et al.. Haplotype analyses of cholesteryl ester transfer protein gene promoter: a clue to an unsolved mystery of TaqIB polymorphism. J Mol Med (Berl) 2003;81:246–55.10.1007/s00109-002-0414-7Suche in Google Scholar PubMed
13. Papp, AC, Pinsonneault, JK, Wang, D, Newman, LC, Gong, Y, Johnson, JA, et al.. Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk. PLoS One 2012;7:e31930.10.1371/journal.pone.0031930Suche in Google Scholar PubMed PubMed Central
14. Boekholdt, SM, Sacks, FM, Jukema, JW, Shepherd, J, Freeman, DJ, McMahon, AD, 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;111:278–87.10.1161/01.CIR.0000153341.46271.40Suche in Google Scholar PubMed
15. de Grooth, GJ, Zerba, KE, Huang, SP, Tsuchihashi, Z, Kirchgessner, T, Belder, R, 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;43:854–7.10.1016/j.jacc.2003.08.056Suche in Google Scholar PubMed
16. Kaman, D, Ilhan, N, Ilhan, N, Akbulut, M. TaqIB and severity of coronary artery disease in the Turkish population: a pilot study. Bosn J Basic Med Sci 2015;15:9–13.10.17305/bjbms.2015.157Suche in Google Scholar PubMed PubMed Central
17. Thompson, A, Di Angelantonio, E, Sarwar, N, Erqou, S, Saleheen, D, Dullaart, RP, et al.. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008;299:2777–88.10.1001/jama.299.23.2777Suche in Google Scholar PubMed
18. Yehya, A, Irshaid, Y, Saleh, AA. Cholesteryl ester transfer protein rs1532624 gene polymorphism is associated with reduced response to statin therapy. Curr Mol Pharmacol 2013;6:156–62.10.2174/18744672113066660037Suche in Google Scholar PubMed
19. Ahn, YI, Kamboh, MI, Aston, CE, Ferrell, RE, Hamman, RF. Role of common genetic polymorphisms in the LDL receptor gene in affecting plasma cholesterol levels in the general population. Arterioscler Thromb 1994;14:663–70.10.1161/01.ATV.14.5.663Suche in Google Scholar PubMed
20. Miserez, AR, Rossi, FA, Keller, U. Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects. Eur J Clin Pharmacol 1994;46:107–14.10.1007/BF00199871Suche in Google Scholar PubMed
21. Streja, L, Packard, CJ, Shepherd, J, Cobbe, S, Ford, I, Group, W. Factors affecting low-density lipoprotein and high-density lipoprotein cholesterol response to pravastatin in the West of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol 2002;90:731–6.10.1016/S0002-9149(02)02599-7Suche in Google Scholar PubMed
22. Khalaf, RA, Al-Rawashdeh, S, Sabbah, D, Abu Sheikha, G. Molecular docking and pharmacophore modeling studies of fluorinated benzamides as potential CETP inhibitors. Med Chem 2017;13:239–53.10.2174/1573406412666161104121042Suche in Google Scholar PubMed
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Artikel in diesem Heft
- Frontmatter
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- No association between LDL receptor and CETP genetic variants and atorvastatin response in Jordanian hyperlipidemic patients
- Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers
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Artikel in diesem Heft
- Frontmatter
- Review
- Impact of environmental toxicants exposure on gut-brain axis in Parkinson disease
- Original Articles
- The effect of nonadherence on phenobarbital concentrations and recommendations on the replacement dose using Monte Carlo simulation
- SLCO1B1 c.521T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients
- Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients
- Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen
- No association between LDL receptor and CETP genetic variants and atorvastatin response in Jordanian hyperlipidemic patients
- Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers
- Potential factors of Helicobacter pylori resistance to clarithromycin
- Letter to the Editor
- Phenylalanine monooxygenase and the ‘sulfoxidation polymorphism’; the salient points
