Abstract 13435: Gender Differences in Impact of CYP2C19 Polymorphism on Risk of Coronary Artery Disease
Background: Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. Specific CYPs, such as CYP2C9 and 2C19, localized in vascular smooth muscle and endothelium may contribute to the pathophysiology of cardiovascular diseases. The aim was to clarify whether CYP2C19 polymorphism would be associated with the development of coronary artery disease (CAD) as a disease-susceptibility gene independently of the conventional coronary risk factors.
Methods: This study enrolled 723 patients with CAD (male 71%, 70yrs), and healthy subjects undergoing medical checkup (n=453) as control (male 69%, 53yrs). CAD was defined as definitive stable angina and acute coronary syndrome. We analyzed the incidence of CYP2C19 polymorphism for presence of CAD in all subjects and in the absence of diabetes, dyslipidemia, and chronic kidney disease (CKD) to minimize the influence of acquired and environmental coronary risk factors. CYP2C19 genotype was classified into 3 genotypes: (1) EM having normal function alleles, (2) IM having one loss-of-function (LOF) allele, and (3) PM having two LOF alleles.
Results: The distribution of CYP2C19 genotype in total subjects between both groups was not different (EM, IM, PM: CAD; 34, 47, 19%: control; 32, 49, 19%). In the analysis of non-diabetes, non-dyslipidemia, and non-CKD status, there was no difference in incidence of CYP2C19 genotype between CAD (n=115) and control (n=194) groups (EM, IM, PM: non-risk CAD, 33, 46, 21%; non-risk control, 31, 52, 17%). When patients were stratified by gender, there was significant difference in distribution of CYP2C19 genotype between male and female in non-risk CAD patients (EM, IM, PM: male; 35, 50, 15%: female; 27, 36, 36%). In short, the PM frequency was significantly higher in female than in male (15% vs. 36%, P=0.011). Moreover, in females between CAD and control, incidence of PM was significantly higher in non-risk CAD patients than in non-risk control (36 vs. 14%, P=0.006), but not in male (16 vs. 19%, P=0.546).
Conclusions: CYP2C19 PM status might be associated with the development of CAD. CYP2C19 polymorphism seems to have an important role in pathophysiology of atherosclerotic disease as a disease-susceptibility gene.
Author Disclosures: S. Hokimoto: None. T. Akasaka: None. K. Nakagawa: None. H. Ogawa: Other Research Support; Modest; AstraZeneca, Astellas, Boehringer lngelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Kowa, MSD, Novartis, Pfizer, Sanofi, Takeda. Other Research Support; Significant; Bayer, Chugai, Otsuka. Honoraria; Modest; AstraZeneca, Bayer, Pfizer, Sanofi, Takeda. Honoraria; Significant; Daiichi Sankyo, MSD.
- © 2014 by American Heart Association, Inc.