Journal of Cardio-Thoracic Medicine

Journal of Cardio-Thoracic Medicine

CYP2C19 Genetic Polymorphism in the East of Iran: Its Association with the Severity and Pattern of Coronary Artery Disease

Document Type : Original Article

Authors
Mahdi Zahedi 1
Mahmoud Shabestari 2
Hossein Ayatollahi 3
Arash Gholoobi 2
1 Interventional Cardiologist, Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
2 Interventional Cardiologist, Atherosclerosis Prevention Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3 Hematopathologist, Department of pathology, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/jctm.2019.38630.1210
Abstract
Introduction: Since there has been a dearth of research on the assessment of CYP2C19 polymorphism in the east of Iran (Khorasan provinces), this study aimed to detect, CYP2C19*2 and CYP2C19*3 allele frequencies among patients with coronary artery disease. The participants were selected among those referring to Emam Reza Hospital, Mashhad, Iran. Furthermore, the current research was motivated to elucidate the association of CYP2C19 polymorphism with the severity and pattern of coronary artery disease.
Material and Methods: This study was conducted on 84 patients who were subjected selective coronary angiography. The participants of the present study were from Khorasan, Iran. The Genotyping of extracted crude DNA for CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) alleles was performed through PCR-RFLP method.
Results: The obtained results of the current study revealed three different allelic band patterns. Out of the 84 individuals, 71 were homozygous for the wild type allele in both exon 5 and exon 4 (wt/wt; 84.5%), 15 were homozygous for the CYP2C19*2 polymorphism (*2/*2;14.3%), and 1 subject was homozygous for the CYP2C19*3 (*3/*3; 1.2%). No subjects were heterozygous for the CYP2C19*2 (wt/*2; 0.0%) or CYP2C19*3 (wt/*3; 0.0%) or heterozygous for the CYP2C19*2 and the CYP2C19*3 mutations (*2/*3; 0.0%). 
Conclusion: The findings of the current study confirmed the existence of CYP2C19 polymorphism among people of Khorasan.
Keywords
Clopidogrel
Coronary Artery Disease
CYP2C19 Polymorphism
  1. Wang H, Qi J, Li Y, Tang Y, Li C, Li J, Han Y. Pharmacodynamics and pharmacokinetics of ticagrelor vs. clopidogrel in patients with acute coronary syndromes and chronic kidney disease. Br J Clin Pharmacol. 2018 Jan; 84(1):88-96.
  2. Holmes D, Dehmer G, Kaul S, Leifer D, O’Gara P, Stein M. ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning”. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2010;56(4):321-341.
  3. Moosavi-Movahedi AA, Golchin AR, Nazari KK, Chamani J, Saboury AA, Bathaie SZ, Tangestani-Nejad S. Microcalorimetry, energetics and binding studies of DNA–dimethyltin dichloride complexes. Thermochim Acta. 2004; 414(2):233-241.
  4. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. New England Journal of Medicine. 2009 Jan 22;360(4):354-62.
  5. Luo HR, Poland RE, Lin KM, Wan YJ. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: A cross‐ethnic comparative study. Clinical Pharmacology & Therapeutics. 2006 Jul 1;80(1):33-40.
  6. Man M, Farmen M, Dumaual C, Teng CH, Moser B, Irie S, Noh GJ, Njau R, Close S, Wise S, Hockett R. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. The Journal of Clinical Pharmacology. 2010 Aug 1;50(8):929-40.
  7. Mirabbasi SA, Khalighi K, Wu Y, Walker S, Khalighi B, Fan W, Kodali A, Cheng G. CYP2C19 genetic variation and individualized clopidogrel prescription in a cardiology clinic. Journal of community hospital internal medicine perspectives. 2017 Jul 3;7(3):151-6.
  8. Anichavezhi   D,   Chakradhara  Rao    US,  Shewade DG, Krishnamoorthy R, Adithan C. Distribution of CYP2C19*17 allele and genotypes in an Indian population. J Clin Pharm Ther. 2012;Jun; 37(3):313-8.
  9. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, Van Den Brand M, Bass EJ, Van Dyck N. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. New England Journal of Medicine. 2009 Mar 5;360(10):961-72.
  10. Chamani J, Heshmati M. Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: spectroscopic and calorimetric approaches. J Colloid Interface Sci. 2008; 322(1):119-127.
  11. Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Büttner HJ, Neumann FJ. Cytochrome P450 2C19 681G> A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. Journal of the American College of Cardiology. 2008 May 20;51(20):1925-34.
  12. Brown SA., Preira N. Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine. J. Pers. Med. 2018; 8(1), 8.
  13. Zolfagharzadeh M, Pirouzi M, Asoodeh A, Saberi M, Chamani J. A comparison investigation of DNP-binding effects to HSA and HTF by spectroscopic and molecular modeling techniques. J Biomol Struct Dyn. 2014; 32(12):1936-1952.
  14. Novkovic M, Matic D, Kusic-Tisma J, Antonijevic N, Radojkovic D, Rakicevic L. Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel. European journal of clinical pharmacology. 2018; 74(4):443-51.
  15. Sanei H, Asoodeh A, Hamedakbari-Tusi S, Chamani J. Multi-spectroscopic investigations of aspirin and colchicine interactions with human hemoglobin: binary and ternary systems. J Solution Chem. 2011;40(11):1905-1931.
  16. Ge H, Lv X, Ren H, Jin H, Jiang Y, He H, Liu P, Li Y. Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling. Journal of neurointerventional surgery. 2017; 9(10):958-62.
  17. Zand N, Tajik N, Hoormand M, Moghaddam AS, Milanian I. Allele Frequency of CYP2C19 Gene Polymorphisms in a Healthy Iranian Population. IJPT. 2005; 4:124-128.

 

 

Journal of Cardio-Thoracic Medicine
Volume 7, Issue 1
Winter 2019
Pages 417-421