Background: Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. Methods and Results: We examined CYP2C19 genotypes in patients with MVA (n=71) and healthy subjects as control (n=71). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of -functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P=0.007) and high sense C-reactive protein (hs-CRP) levels (0.127±0.142 vs. 0.086±0.097mg/dL; P=0.043) than that of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180±0.107 vs. 0.106±0.149mg/dL, P=0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM (10.9±1.64 vs. 14.2±5.39ng/mL, P=0.019 (11,12-DHET); 15.2±4.39 vs. 17.9±4.73ng/mL, P=0.025 (14,15-DHET)). Conclusions: CYP2C19 variants is associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.
- genetic polymorphism
- microvascular angina
- epoxyeicosatrienoic acid
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology