Cytochrome P450 Genetic Variants and Their Metabolite Levels Associated with Plaque Stability in Patients with Ischemic Stroke.

Abstract

Cytochrome P450s (CYP450) enzymes regulate inflammation and atherosclerosis and can affect carotid plaque stability in patients with ischemic stroke (IS). This study aimed to investigate the association of CYP450 genetic variants with CYP plasma metabolite levels and plaque stability in patients with IS. Eleven single nucleotide polymorphisms (SNPs) of CYP genes and their plasma metabolite [20-hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] levels were measured in 396 patients with IS who underwent high-resolution B-mode ultrasound carotid plaque detection and were stratified into the following groups: non-carotid plaque and carotid plaque groups. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP). Among the 396 patients with IS, 294 cases (74%) had plaques. The frequency of rs17110453CC, rs751141 GG, and rs9333025 GG genotypes was significantly higher in patients with plaque than those without plaque. The CC, GG, GG, and GG genotypes of rs17110453, rs776746, rs751141, and rs9333025 polymorphisms were independently associated with ELP (OR, 2.62 [1.34-5.26]; OR, 1.89 [1.16-3.58]; OR, 3.12 [1.27-7.13]; and OR, 2.06 [1.34-6.33], respectively). These polymorphisms were also associated with CYP plasma metabolite levels. Patients with ELP have also shown significantly higher levels of 20-HETE and DiHETEs, but lower levels of EETs. Our data demonstrates that CYP450 SNPs are associated with plasma CYP450 metabolite levels and echolucent plaques, indicating that these SNPs may be potential markers for plaque instability.