Have a personal or library account? Click to login
Association of CYP2C19*2 c.681G>A (rs4244285) Loss-of-function Allele with Cardiovascular Disease Risk in the Kosovo Population Cover

Association of CYP2C19*2 c.681G>A (rs4244285) Loss-of-function Allele with Cardiovascular Disease Risk in the Kosovo Population

Open Access
|Mar 2025

References

  1. Abubakar M, Raza S, Hassan KM, Javed I, Hassan KM, Farrukh F, et al. Efficacy, safety, and role of antiplatelet drugs in the management of acute coronary syndrome: a comprehensive review of literature. Cureus. 2023;15(3):e36335.
  2. Chandiramani R, Spirito A, Johnson JW, Mehta A, Vogel B, Faillace RT, et al. Antiplatelet therapy for coronary artery disease in 2023: current status and future prospects. Expert Rev Cardiovasc Ther. 2023;21(5):311-28.
  3. Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, et al. CYP2C19 genotype prevalence and association with recurrent myocardial infarction in British-South Asians treated with clopidogrel. JACC Adv. 2023;2(7):100573.
  4. Sangkuhl K, Klein TE, Altman RB. Clopidogrel pathway. Pharmacogenet Genomics. 2010;20(7):463-5.
  5. Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376(9749):1312-9.
  6. Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304(16):1821-30.
  7. Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010;376(9749):1320-8.
  8. Chen YW, Liao YJ, Chang WC, Hsiao TH, Lin CH, Hsu CY, et al. CYP2C19 loss-of-function alleles predict clinical outcomes in East Asian patients with acute myocardial infarction undergoing percutaneous coronary intervention and stenting receiving clopi-dogrel. Front Cardiovasc Med. 2022;9:994184.
  9. Wang T, Feng J, Zhou L, Zhao T, Zhang H, Shen H, et al. The cytochrome P450 2C19 polymorphism associated with major adverse cardiovascular events risk in Kazak patients undergoing percutaneous coronary intervention and receiving clopidogrel. Endocr Metab Immune Disord Drug Targets. 2023;23(2):196-204.
  10. Pereira NL, Cresci S, Angiolillo DJ, Batchelor W, Capers IV Q, Cavallari LH, et al. CYP2C19 genetic testing for oral P2Y12 inhibitor therapy: a scientific statement from the American Heart Association. Circulation. 2024;150(6):e129-50.
  11. Beitelshees AL, Thomas CD, Empey PE, Stouffer GA, Angiolillo DJ, Franchi F, et al. CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention in diverse clinical settings. J Am Heart Assoc. 2022;11(4):e024159.
  12. Claassens DMF, Vos GJA, Bergmeijer TO, Herma-nides RS, Hof AWJ van’t, Harst P van der, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019;381(17):1621-31.
  13. Kleindorfer DO, Towfighi A, Chaturvedi S, Cock-roft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-467
  14. Gower MN, Ratner LR, Williams AK, Rossi JS, Stouffer GA, Lee CR. Clinical utility of CYP2C19 genotype-guided antiplatelet therapy in patients at risk of adverse cardiovascular and cerebrovascular events: a review of emerging evidence. Pharmgenom-ics Pers Med. 2020;13:239-52.
  15. Baudhuin LM, Train LJ, Goodman SG, Lane GE, Lennon RJ, Mathew V, et al. Point-of-care CYP2C19 genotyping after percutaneous coronary intervention. Pharmacogenomics J. 2022;22(5-6):303-7.
  16. Russmann S, Rahmany A, Niedrig D, Hatz KD, Ludin K, Burden AM, et al. Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice. Eur J Clin Pharmacol. 2021;77(5):709-16.
  17. Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022;112(5):959-67.
  18. Abdullah-Koolmees H, Van Keulen AM, Nijen-huis M, Deneer VH. Pharmacogenetics guidelines: overview and comparison of the DPWG, CPIC, CPNDS, and RNPGx guidelines. Front Pharmacol. 2021;11:595219.
  19. Saiz-Rodríguez M, Belmonte C, Caniego JL, Koller D, Zubiaur P, Bárcena E, et al. Influence of CYP450 enzymes, CES1, PON1, ABCB1, and P2RY12 polymorphisms on clopidogrel response in patients subjected to a percutaneous neurointervention. Clin Ther. 2019;41(6):1199-1212.e2.
  20. Du P, Li X, Li D, Ma Y, Ni M, Li Y, et al. PEAR1, PON1, CYP2C19, CYP1A2 and F2R polymorphisms are associated with MACE in clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention. Pharmgenomics Pers Med. 2024;17:611-21.
  21. Eken E, Estores DS, Cicali EJ, Wiisanen KK, Johnson JA. A pharmacogenetics-based approach to managing gastroesophageal reflux disease: current perspectives and future steps. Pharmgenomics Pers Med. 2023;16:645-64.
  22. Biswas M, Rahaman S, Biswas TK, Ibrahim B. Risk of major adverse cardiovascular events for concomitant use of clopidogrel and proton pump inhibitors in patients inheriting CYP2C19 loss-of-function alleles: meta-analysis. Int J Clin Pharm. 2021;43(5):1360-69.
  23. Wang J, Kuang J, Yi Y, Peng C, Ge Y, Yin S, et al. Does CYP2C19 polymorphisms affect neurological deterioration in stroke/TIA patients?: a systematic review and meta-analysis of prospective cohort studies. Medicine (Baltimore). 2021;100(11):e25150.
  24. Mugosa S, Radosavljevic I, Sahman M, Djordjevic N, Todorovic Z. Risk factors for adverse drug reactions associated with clopidogrel therapy. Open Med (Wars). 2022;17(1):694-701.
  25. Cavallari LH, Limdi NA, Beitelshees AL, Lee JC, Duarte JD, Franchi F, et al. Evaluation of potential racial disparities in CYP2C19-guided P2Y12 inhibitor prescribing after percutaneous coronary intervention. Clin Pharmacol Ther. 2023;113(3):615-23.
  26. Nguyen AB, Cavallari LH, Rossi JS, Stouffer GA, Lee CR. Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy. Front Cardiovasc Med. 2022;9:991646.
  27. Krasniqi V, Dimovski A, Bytyqi HQ, Eftimov A, Šimičević L, Božina N. Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population. Arch Ind Hyg Toxicol. 2017;68(3):180-84.
  28. Castrichini M, Luzum JA, Pereira N. Pharmacogenetics of antiplatelet therapy. Annu Rev Pharmacol Toxicol. 2023;63:211-29.
  29. Kapedanovska Nestorovska A, Jakovski K, Nau-movska Z, Bajro MH, Sterjev Z, Eftimov A, et al. Distribution of the most common genetic variants associated with a variable drug response in the population of the Republic of Macedonia. Balkan J Med Genet. 2015;17(2):5-14.
  30. Petrović J, Pešić V, Lauschke VM. Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. Eur J Hum Genet. 2020;28:88-94.
  31. Vidović S, Škrbić R, Stojiljković MP, Vidović V, Bećarević J, Stoisavljević-Šatara S, et al. Prevalence of five pharmacologically most important CYP2C9 and CYP2C19 allelic variants in the population from the Republic of Srpska in Bosnia and Herzegovina. Arh Hig Rada Toksikol. 2021;72(3):129-34.
  32. Kapedanovska-Nestorovska A, Dimovski AJ, Sterjev Z, Geskovska NM, Suturkova L, Ugurov P, et al. The AKR1D1*36 (rs1872930) allelic variant is independently associated with clopidogrel treatment outcome. Pharmgenomics Pers Med. 2019;12:287-95.
  33. Bačković D, Ignjatović S, Rakićević L, Kušić-Tišma J, Radojković D, Čalija B, et al. Influence of CY-P2C19*2 gene variant on therapeutic response during clopidogrel treatment in patients with carotid artery stenosis. J Med Biochem. 2016;35(1):26-33.
  34. Petranovic MZ, Tomas Z, Skaric-Juric T, Narancic NS, Janicijevic B, Salihovic MP. The variation of CYP2C19 gene in the Roma population from Croatia. Med Biol. 2018;1(2):32-37.
  35. Sarkis A, Roman RJ. Role of cytochrome P450 metabolites of arachidonic acid in hypertension. Curr Drug Metab. 2004;5(3):245-56.
  36. Shahabi P, Siest G, Meyer UA, Visvikis-Siest S. Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders. Pharmacol Ther. 2014;144(2):134-61.
  37. Rothenbacher D, Hoffmann MM, Breitling LP, Rajman I, Koenig W, Brenner H. Cytochrome P450 2C19*2 polymorphism in patients with stable coronary heart disease and risk for secondary cardiovascular disease events: results of a long-term follow-up study in routine clinical care. BMC Cardiovasc Disord. 2013;13:1-11.
  38. Zhang YY, Zhou X, Ji WJ, Liu T, Ma J, Zhang Y, et al. Association between CYP2C19*2/*3 polymorphisms and coronary heart disease. Curr Med Sci. 2019;39:44-51.
  39. Cai N, Li C, Gu X, Zeng W, Zhong J, Liu J, et al. CY-P2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a casecontrol study. BMC Cardiovasc Disord. 2023;23:185.
  40. Martínez-Quintana E, Rodríguez-González F, Medina-Gil JM, Garay-Sánchez P, Tugores A. CYP2C19 activity and cardiovascular risk factors in patients with an acute coronary syndrome. Med Clin (Barc). 2017;149(6):235-39.
  41. Chen W, Liu Y, Deng X, Li B, Wang H, Wei G, et al. CYP2C19 loss-of-function is an associated risk factor for premature coronary artery disease: a case-control study. Int J Gen Med. 2024;17:5049-58.
Language: English
Page range: 77 - 85
Published on: Mar 6, 2025
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year

© 2025 N Elshani, K Ukella, Stojovska M Staninova, Z Naumovska, M Kurshumliu, D Gorani, Nestorovska A Kapedanovska, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.