POLYMORPHISM OF CYTOCHROME P450 EPOXYGENASE AND ITS ASSOCIATION WITH ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE
Journal Title: INTERNATIONAL JOURNAL OF PURE MEDICAL RESEARCH - Year 2017, Vol 2, Issue 4
Abstract
Background: Cytochrome P450 (CYP) epoxygenase metabolise arachidonic acid (AA) into four epoxyeicosatrienoic acids (EETs) 5,6- EETs, 8,9 EETs, 11,12-EETs and 14,15-EETs. Since, EETs are unstable eicosanoids they rapidly get converted into dihydroxyeicosanoid trienoicacids (DHETs) by soluble hydrolase. These eicosanoids promote defence mechanism against inammatory atherosclerosis process. However, 11,12-EETs are more potent eicosanoids in maintaining anti-atherosclerotic activity. Endothelial dysfunction is the key step in the pathogenesis of atherosclerosis. Polymorphism in CYP epoxygenase can alter individual's risk for events in coronary artery disease (CAD) patients. Therefore, we examined the impact of CYP epoxygenase polymorphism indirectly through evaluation of 11,12-DHET levels and its association with endothelial dysfunction. Methods: It is a prospective case-control study consisting of 84 acute coronary syndrome (ACS) patients and 84 healthy controls of either gender aged above 18 years. Fasting serum lipid prole including total cholesterol ( TC), high density lipid (HDL), triglycerides (TG) and homocysteine levels were measured in all subjects. We measured plasma 11,12-dihydroxyeicosatrienoic acid (11,12-DHET) as indicative of 11,12-EETs. Genotyping of CYP putative exons of CYP2C9, CYP2C19 and CYP2J2 epoxygenase were carried out by Polymerase Chain Reaction–Single Strand Conformation Polymorphism (PCR-SSCP) method. Sanger's sequencing chain termination method was carried out for SSCP positive samples. All the data obtained were analysed by using Ms- Excel, 2007 and SPSS, version 24.Software, IBM, USA. Results: We observed signicantly higher levels of homocysteine in CAD group (35.1 ± 13.8 μmol/L) indicating higher inammatory condition in patients compared to control group (8.1 ± 2.9 μmol/L, p < 0.001). We also found higher 11,12-DHET levels in CAD group (628.6 ± 324.3 pg/mL) compared to healthy controls (332.1 pg/mL ± 203.2 pg/mL, p = 0.0001). In this connection, we observed positive correlation between homocysteine levels and 11,12- DHETs in CAD group (p = 0.01). Genotyping of CYP exons revealed 11 patients (13%) reporting 12 single nucleotide polymorphisms (SNPs). We found signicant difference in the levels of 11,12- DHETs between the patients reporting CYP polymorphism and patients without CYP polymorphism compared with the control (p<0.001). Further, we observed negative correlation between homocysteine levels and 11,12-DHETs in CAD patients reporting CYP polymorphisms indicating decline of DHET mediated anti-atherosclerotic activity Conclusions: Presence of lower levels of 11,12- DHETs is a reection of poor reserve defence mechanism in CAD patients that might cause endothelial dysfunction and risk of cardiac events. Therefore, genotyping of CYP2C9, CYP2C19 and CYP2J2 genes can be recommended to be used as prognostic marker for risk stratication in CAD patients.
Authors and Affiliations
Sowjenya Gopal, Rajasekhar Durgaprasad, Vanajakshamma Velam, Srinivasa Rao P. V. L. N, Sarma P. V. G. K
Keywords
Related Articles
- EP ID EP597500
- DOI -
- Views 63
- Downloads 0
DOPAMINE D2 RECEPTOR GENE POLYMORPHISMS AND EXTERNALIZING BEHAVIORS IN CHILDREN AND ADOLESCENTS
Dopamine is involved in several cerebral physiological processes, and single nucleotide polymorphisms (SNP) in the dopamine D2 receptor gene (DRD2) have been associated with numerous neurological and mental disorders. Th...
ISOLATION OF LACTIC ACID BACTERIA PRODUCING MANNITOL FROM INDONESIAN COCOA BEANS FERMENTATION
Mannitol is a polyol which is widely used in many industries. Lactic acid bacteria known as one of microorganism which produce mannitol in a certain condition. LABs are widely found in fermentation product. This research...
HYPERLIPIDEMIA IN DIABETIC AND HYPOTHYROID PATIENTS: CASE CONTROL STUDY
BACKGROUND: Hyperlipidemia is the leading cause of death in the CVD patients. Diabetes and hypothyroidism are the two main endocrine risk factors for hyperlipidemia. Diabetes is associated with altered metabolism of trig...
FANTASTIC FRUITY PEBBLES: THE CANCERPROTECTIVE ROLE OF ARTIFICIAL COLORING IN BREAKFAST CEREALS
The purpose of this study is to examine the role that articial coloring has in breakfast cereals. In breakfast cereals, we examine articial coloring. Rigorous statistical analysis was performed. We nd that articial c...
THE EFFECT OF INTENSIVE TRAINING AND PHYSICAL ACTIVITY PROGRAM ON PHYSICAL CAPACITY IN PEOPLE WITH SPINAL CORD INJURY
Background Physical activity levels are generally low after SCI. The promotion of regular physical activity into daily life is one of the main aspirations of society. Objective To determine the effectiveness of two-week...