Endothelial NO Synthase Polymorphic Gene in Coronary Artery Dilation Disease

NCT ID: NCT06220682

Last Updated: 2024-01-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2022-06-30

Brief Summary

Introduction: The coronary artery dilatations disease (Coronary artery aneurysm/coronary artery ectasia) characterized by inappropriate coronary artery dilations. (c.894G>T) is a gene polymorphism that may decreases eNOS enzyme activity which increases the risk for coronary heart disease by affecting released (NO) molecules. One of the most researched variations in eNOS gene is c.894G>T polymorphism, which changes amino acid sequence at position 298 from Glu (GAG) to Asp (GAT), nevertheless, its role in Coronary dilatations disease still uncertain.

Aim of study: To study correlation between the c.894G>T gene polymorphism and angiographically dilated coronary artery (CAA/CAE), as well as to determine whether there is any association between this polymorphism and atherosclerotic CAD.

Methodology: A comparative study on 100 patients with acute coronary syndrome who underwent coronary angiography from December 2020 to June 2022. According to standard angiographic views and expert opinions, patients were divided as, 25 patients normal, 25 patients had only atherosclerotic coronary artery disease, 25 patients had dilated coronaries (CAA/CAE) without atherosclerosis and 25 patients had dilated coronaries with atherosclerotic coronary artery disease. The specific genetic PCR laboratory test were performed for eNOS SNPs (single nucleotide polymorphism) namely, 894G > T (Glu298Asp; rs 1799983), using Real-Time PCR.

Detailed Description

Aim of Work We aim at determining the potential correlations between polymorphism of nitric oxide gene (c.894G>T) and angiographically dilated coronary arteries (coronary artery aneurysm or ectasia), as well as to determine if there is any link to atherosclerotic coronary diseases (ACAD).

Methodology:

Based on standard coronary angiographic views, two experienced independent operators evaluated the presence of coronary artery dilatations (CAA, CAE) and associated atherosclerotic CAD in all patients' angiograms.

Inclusion criteria Patients who have angiographically coronary artery dilatations (coronary artery aneurysm or ectasia) (CAA/CAE) with or without angiographic evidence of atherosclerotic CAD.

Another group of patients with angiographically normal or atherosclerotic coronaries without evidence of dilatation.

Exclusion criteria Patients with secondary coronary dilatations after balloon angioplasty, coronary stent implantation, patients with coronary artery bypass surgery who have post CABG native coronary dilatations, all were excluded from this study.

Definitions CAE refers to a diffuse dilatation affecting more than 1/3 of length of CA where its diameter is 1.5 greater than subsequent healthy coronary portion [1, 2, 3].

CAA is less common clinical finding that is described as dilation at the CAs that is < 1/3 of the length of the CA also with diameter 1.5 greater than normal length of nearby part [1, 2, 3, 4].

Laboratory method and genetic analysis The specific genetic PCR laboratory test were performed for all selected patients for eNOS SNPs (single nucleotide polymorphism) namely, 894G > T (Glu298Asp; rs 1799983), using Real-Time PCR (QuantStudioTM 3 Real-Time PCR) with an allele-specific fluorogenic oligonucleotide probe and a TaqMan pre-designed SNP Genotyping assay (TaqMan technique; Applied Biosystems, Germany), The fluorogenic dyes employed to achieve allelic discrimination were FAM (6-carboxy-fluorescein) and VIC (Applied Biosystems proprietary dye). a total reaction volume of 25 L (12.5L TaqMan® Genotyping Master Mix) (2x) - 1.25 µL TaqMan genotyping assay(20x) -5.0µL genomic DNA- 6.25µL DNase-free, RNasefree water) is used to perform PCR.

Primary outcome: To study correlation between the c.894G>T gene polymorphism and angiographically dilated coronary artery (CAA/CAE) Secondary outcome: To determine whether there is any association between this polymorphism and atherosclerotic CAD.

Statistical analysis SPSS v.21 statistical package was used to code and entering data, where it described as number and percent for qualitative mean and standard deviation (SD) for normally distributed data while median and inter quintile rang (IQR) chosen for non-normally distributed quantitative data.

Comparisons for qualitative variables between groups was mad by chi-square or fissure exact tests, while comparisons across normally distributed quantitative variables were done using analysis of variance and post hock 2khs test, and quantitative variables which is not normally distributed, where compared using (non-parametrical croscal wise and Mann-Whitney u tests), statistically significant considered when P. values was below or equal (0.05).

Conditions

Coronary Artery Ectasia

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

normal group

25 patients angiographically normal coronaries

The specific genetic PCR laboratory test were performed for all selected patients for eNOS SNPs

Intervention Type: DIAGNOSTIC_TEST

using Real-Time PCR (QuantStudioTM 3 Real-Time PCR) with an allele-specific fluorogenic oligonucleotide probe and a TaqMan pre-designed SNP Genotyping assay

atherosclerotic non dilated group

25 patients angiographically had atherosclerotic plaques with no coronary dilatations

No interventions assigned to this group

dilated non atherosclerotic group

25 patients angiographically involved coronary dilatations with no atherosclerotic plaques

No interventions assigned to this group

dilated atherosclerotic group

25 patients angiographically had both coronary dilatations and atherosclerotic plaques

The specific genetic PCR laboratory test were performed for all selected patients for eNOS SNPs

Intervention Type: DIAGNOSTIC_TEST

using Real-Time PCR (QuantStudioTM 3 Real-Time PCR) with an allele-specific fluorogenic oligonucleotide probe and a TaqMan pre-designed SNP Genotyping assay

Interventions

The specific genetic PCR laboratory test were performed for all selected patients for eNOS SNPs

using Real-Time PCR (QuantStudioTM 3 Real-Time PCR) with an allele-specific fluorogenic oligonucleotide probe and a TaqMan pre-designed SNP Genotyping assay

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

Patients who have angiographically coronary artery dilatations (coronary artery aneurysm or ectasia) (CAA/CAE) with or without angiographic evidence of atherosclerotic CAD.

Another group of patients with angiographically normal or atherosclerotic coronaries without evidence of dilatation.

Exclusion Criteria

Patients with secondary coronary dilatations after balloon angioplasty, coronary stent implantation, patients with coronary artery bypass surgery who have post CABG native coronary dilatations, all were excluded from this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Mostafa Farouk

Lecturer of critical care

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Mowafy, MD

Role: STUDY_CHAIR

Cairo University

Locations

Cairo university

Cairo, , Egypt

Countries

Egypt

Other Identifiers

Kasralainy school of medicine

Identifier Type: -

Identifier Source: org_study_id