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Published yearly: 

4 Issues

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ISSN: 2320-964X (Online) 

ISSN: 2320-7817  (Print)

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Editor-in-Chief

Dr. Santosh Pawar 


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RESEARCH ARTICLE

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Int. Journal of Life Sciences, 2018; 6(2): 477-486       |                 Available online, April 26, 2018

Polymorphism of Cytochrome P450 epoxygenase and its association with Endothelial Dysfunction in Patients with Coronary Artery Disease 

Gopal Sowjenya  1Durgaprasad Rajasekhar  1 , Velam Vanajakshamma1, PVLN Srinivasa Rao2 ,

PVGK Sarma 3

 

1Department   of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati, A.P.

2Department   of   Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, A.P.

3Department   of   Biotechnology, Sri Venkateswara Institute of Medical Sciences, Tirupati, A.P.

*Corresponding Author: Dr. D. RAJASEKHAR, M.D., D.M., FACC., FESC., FSCAI., Senior Professor and Head, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517507, A.P. Phone: +91-9849221650   |    E-mail: drdrsekhar@gmail.com

 

Received : 05.02.2018     |            Accepted : 29.03.2018     |       Published : 26.04.2018

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 dihydroxy eicosa trienoicacids (DHETs) by Soluble epoxy hydrolase (sEH). These eicosanoids promote defence mechanism against inflammatory 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 profile 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 chain termination sequencing 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 significantly higher levels of  homocysteine in CAD group (35.1 ± 13.8 µmol/L) indicating higher inflammatory 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 significant 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 reflection 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 stratification in CAD patients.

 

Keywords: Polymorphism, Cytochrome P450 epoxygenase, Endothelial function and Acute coronary syndrome patients.

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Editor: Dr.Arvind Chavhan

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Cite this article as:

Gopal Sowjenya, Durgaprasad Rajasekhar, Velam Vanajakshamma, PVLN Srinivasa Rao, PVGK Sarma(2018) Polymorphism of Cytochrome P450 epoxygenase and its association with Endothelial Dysfunction in Patients with Coronary Artery Disease, Int. J. of. Life Sciences, Volume 6(2): 477-486. 

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Acknowledgement:

We gratefully thank Sri Balaji Arogya Varaprasadini (SBAVP) scheme of our institution for partial financial support to carry out this work.

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Conflicts of interest: The authors stated that no conflicts of interest.

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Copyright: © 2018 | Author(s), This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial - No Derives License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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