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Association between CYP2C19*2/*3 Polymorphisms and Coronary Heart Disease.

Ying-Ying Zhang1,2, Xin Zhou3, Wen-Jie Ji3

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The CYP2C19*2 gene variant increases coronary heart disease (CHD) risk and adverse cardiovascular events in patients. This genetic factor is a significant predictor of CHD presence and post-discharge complications.

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clopidogrelcoronary heart diseasecytochrome P450 2C19polymorphisms

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Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Cytochrome P450 2C19 (CYP2C19) plays a role in drug metabolism and has been linked to various health conditions.
  • Genetic variations, specifically single nucleotide polymorphisms (SNPs), can influence individual susceptibility to diseases like coronary heart disease (CHD).
  • The CYP2C19*2 and *3 polymorphisms are common and their impact on CHD development and clinical outcomes warrants investigation.

Purpose of the Study:

  • To investigate the association between CYP2C19*2/*3 polymorphisms and the incidence of coronary heart disease (CHD).
  • To evaluate the influence of these polymorphisms on the occurrence of adverse clinical events in patients with CHD.
  • To identify independent predictors of CHD and adverse cardiovascular events.

Main Methods:

  • A cohort of 231 patients undergoing percutaneous coronary intervention were genotyped for CYP2C19*2 (681G>A) and *3 (636G>A) polymorphisms.
  • Coronary angiography was used to diagnose CHD.
  • Adverse clinical events were monitored over a 14-month follow-up period.
  • Statistical analyses, including binary logistic regression and Cox proportional hazards models, were employed.

Main Results:

  • CYP2C19*2 carriers exhibited a significantly higher incidence of CHD (P=0.025).
  • CYP2C19*2 carriage and male gender were identified as independent predictors of CHD presence (OR 1.94, P=0.028 and OR 2.74, P=0.001, respectively).
  • Patients with CYP2C19*2 polymorphisms had a significantly higher rate of adverse cardiovascular events within 14 months (21.6% vs. 6.3%, P=0.019).
  • CYP2C19*2 loss-of-function was the sole independent predictor of coronary events during follow-up (OR=3.65, P=0.036).
  • No significant influence of the CYP2C19*3 mutation was observed in the Chinese Han population.

Conclusions:

  • The CYP2C19*2 polymorphism is associated with an increased risk of developing CHD.
  • CYP2C19*2 carriers are at higher risk for adverse cardiovascular events following percutaneous coronary intervention.
  • CYP2C19*2 loss-of-function is a significant independent predictor of adverse outcomes in CHD patients, while CYP2C19*3 does not show a similar association in this population.