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Gender Differences in Impact of CYP2C19 Polymorphism on Development of Coronary Artery Disease

Hokimoto, Seiji MD, PhD*; Tabata, Noriaki MD*; Akasaka, Tomonori MD*; Arima, Yuichiro MD, PhD*; Kaikita, Koichi MD, PhD*; Morita, Kazunori BS; Kumagae, Naoki BS; Oniki, Kentaro MS; Nakagawa, Kazuko MD, PhD; Ogawa, Hisao MD, PhD*

Journal of Cardiovascular Pharmacology: February 2015 - Volume 65 - Issue 2 - p 148–152
doi: 10.1097/FJC.0000000000000171
Original Article

Abstract: The aim was to clarify whether CYP2C19 polymorphism is associated with the development of coronary artery disease (CAD). This study enrolled 723 patients with CAD (men 71%, 70 years) and healthy subjects undergoing a medical checkup (n = 453) as controls (men 69%, 53 years). We analyzed the incidence of CYP2C19 polymorphism and its association with the development of CAD in the absence of diabetes, dyslipidemia, and chronic kidney disease to minimize the influence of conventional coronary risk factors. In the analysis without risk factors, there was no difference in the incidence of the CYP2C19 genotype between CAD (n = 115) and control (n = 194) groups [extensive metabolizer, intermediate metabolizer, poor metabolizer (PM) in non-risk CAD: 33%, 46%, 21%, respectively; in non-risk control: 31%, 52%, 17%, respectively]. Analysis between CAD and control groups by the χ2 test showed that there was significant difference in distribution of CYP2C19 genotype in women alone (P = 0.025) but not in total subjects (P = 0.471) or men (P = 0.678), respectively. CYP2C19 PM was an independent predictor of CAD risk in women alone (odds ratio, 10.717; 95% confidence interval, 1.753–65.505; P = 0.010) but not in men. CYP2C19 PM status might be associated with the development of CAD as a disease susceptibility gene, especially in women.

*Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Japan; and

Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.

Reprints: Seiji Hokimoto, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto City 860-8556, Japan (e-mail:

Supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

The authors report no conflicts of interest.

Received July 10, 2014

Accepted September 12, 2014

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