title: CYP 450 2C19 polymorphisms in Indian patients with coronary artery disease.
abstract: BACKGROUND
  Dual antiplatelet therapy is the cornerstone in the management of acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads to clopidogrel non-responsiveness and may influence clinical outcomes. These polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary artery disease (CAD) have not been studied in Indian population.
  
  
  METHODS
  We studied 110 consecutive patients (mean age 55.7 ± 10.7 years; 90% male) taking clopidogrel with angiographically proven CAD for various genetic polymorphisms in CYP2C19 gene. Relationship between loss of function mutation and clinical presentation with recurrent ACS including ST was analyzed.
  
  
  RESULTS
  Out of 110 patients, 26 (23.64%) had normal genotype, 52 (47.23%) had loss of function mutation *2 and 39 (35.45%) had a gain of function mutation *17, 7 (6.36%) patients were undefined metabolizers (*2/*17) which were excluded from analyses. Final analyses included 103 patients, with 45 (40.90%) having loss of function. Overall 51 patients had ACS, with 27 developing recurrence while on clopidogrel. The prevalence of loss of function mutation was no different between the group with recurrences and those without recurrences (55.6% vs. 50%, p = 0.7). Two patients developed ST while on clopidogrel; both had loss of function mutation.
  
  
  CONCLUSIONS
  CYP2C19 gene polymorphisms are common in Indian population. Loss of function mutation status did not affect the clinical outcomes. A larger study also considering P2Y12 receptor polymorphisms together with platelet activity testing, may be required to establish the role of CYP2C19 gene polymorphisms in clinical practice.
authors.affiliation: Senior Resident, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sudhir S
authors.initials: SS
authors.lastname: Shetkar
authors.affiliation: Associate Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sivasubramanian
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Additional Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Seth
authors.affiliation: AceProbe Technologies (India) Pvt. Ltd., New Delhi 110005, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Chandna
authors.affiliation: Assistant Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Verma
authors.affiliation: Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: balrambhargava@gmail.com.
authors.forename: Balram
authors.initials: B
authors.lastname: Bhargava
authors.affiliation: Professor, Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Bahl
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D021983:Cyclophilins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D062606:Tertiary Care Centers; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000077144:Clopidogrel; D021983:Cyclophilins; C102923:PPIG protein, human; D013988:Ticlopidine
keywords: CYP2C19 polymorphism; Clopidogrel; Coronary artery disease