Association Between Some Polymorphisms in Apelin/ Apelin Receptor Genes and Coronary Artery Disease in Syrian Patients

Study Overview
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Brief Summary
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The apelin-APJ signaling pathway has emerged as an important novel mediator of cardiovascular control and blood pressure homeostasis. Genetic variation in apelin and its receptors likely contributes to essential hypertension, in addition to a range of traditional risk factors. Thus, a study will be conducted on Syrian patients with hypertension and coronary artery disease to investigate some of the single polymorphisms in the apelin gene and its receptor that may be responsible for the development of these diseases, and to link the levels of this peptide and its receptor in the blood with these polymorphisms and the percentage of these diseases (as shown by many Modern Global Reference Studies).

Detailed Description
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Blood levels of apelin and its receptor will be determined in patients and controls, and correlated with hypertension and coronary artery disease. And the allelic and genotypic frequencies of the G212A single polymorphism nucleotide of the apelin receptor gene and the -1860T>C single polymorphism nucleotide of the apelin gene in the study groups. And evaluation the functional role of A allele in hypertension. As well as investigating the association between: the genotypes of the apelin gene and the levels of apelin in the plasma, the genotypes of the apelin receptor gene and the levels of APJ in the plasma in the study groups. And link the polymorphism of the apelin gene with the polymorphism of the apelin receptor gene. And to determine the correlation between the presence of the studied SNPs and some traditional risk factors for coronary artery disease, which are age, hypertension, the onset age of hypertension, smoking, BMI, cholesterol and triglyceride levels in the blood, and family history of CAD.

Official Title
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Investigation of Association Between Single Nucleotide Polymorphisms in Genes of the Apelin/ APJ System (-1860T>C & G212A) and CAD Risk and Hypertension in Syrian Patients

Conditions
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Hypertension, Coronary Artery Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Control group: the subjects were characterized by no history of angina and other heart disease or hypertension, and do not have other chronic or inflammatory diseases. They represent a normal resting ECG and normal exercise ECG stress testing. And the angiography showed the absence of any stenosis of the coronary arteries. They were matched with CAD patients according to age, gender and ethnicity. CAD group with essential hypertension: the subjects were characterized by at least 70% stenosis in any coronary artery and high blood pressure (the average of three blood pressure readings was at least 140 mmHg systolic or 90 mmHg diastolic). CAD group without essential hypertension: the subjects were characterized by at least 70% stenosis in any coronary artery and normal blood pressure. Hypertension group without CAD: the subjects were characterized by the normal coronary artery and high blood pressure. And they were characterized by no history of angina and other heart disease or hypertension, and do not have other chronic or inflammatory diseases. Exclusion Criteria: Individuals with valvular heart disease, cardiomyopathy, chronic kidney disease, diabetes, and inflammatory disease were excluded

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control group<br>subjects who do not have any heart disease, hypertension, or other chronic &inflammatory diseases, and their coronary arteries are normal | |
| CAD group with essential hypertension<br>subjects who have stenosis (at least 70%) of one of the main coronary arteries or its branches and have high blood pressure | |
| CAD group without essential hypertension<br>subjects who have stenosis (at least 70%) of one of the main coronary arteries or its branches and have normal blood pressure | |
| Hypertension group without CAD<br>the subjects were characterized by the normal coronary artery and high blood pressure | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood apelin concentrations | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1000 g for 10 min, then plasma specimens were stored at -80°C until analysis. | Collecting blood samples before angiography | 
| Blood apelin receptor (APJ) concentrations | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1000 g for 10 min, then plasma specimens were stored at -80°C until analysis | Collecting blood samples before angiography | 
| The allelic and genotypic frequencies of the -1860T>C single polymorphism nucleotides of the apelin genes | Genomic DNA will be extracted from peripheral blood sample, after that DNA will be stored in a deep freezer (-80°C) until the genetic analysis | Collecting blood samples before angiography | 
| The allelic and genotypic frequencies of the G212A single polymorphism nucleotides of the apelin receptor genes | Genomic DNA will be extracted from peripheral blood sample, after that DNA will be stored in a deep freezer (-80°C) until the genetic analysis. | Collecting blood samples before angiography | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI | measurement of body weight and height will be recorded to calculate the body mass index | before angiography | 
| Measurement of blood pressure | Hypertension was diagnosed when the average of three blood pressure readings was at least 140 mmHg systolic or 90 mmHg diastolic, or in the event the individuals were taking antihypertensive medication | before angiography | 
| Plasma levels of triglycerides (TG) | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1750 g for 10 min, then plasma specimens were stored at -80°C until analysis | Collecting blood samples before angiography | 
| total cholesterol (TC) levels in plasma | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1750 g for 10 min, then plasma specimens were stored at -80°C until analysis | Collecting blood samples before angiography | 
| high-density lipoprotein cholesterol (HDL-C) levels in plasma | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1750 g for 10 min, then plasma specimens were stored at -80°C until analysis | Collecting blood samples before angiography | 
| low-density lipoprotein cholesterol (LDL-C) | Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 1750 g for 10 min, then plasma specimens were stored at -80°C until analysis | Collecting blood samples before angiography | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apelin, Apelin receptor (APJ), Coronary Artery Disease (CAD), Hypertension, apelin -1860T>C polymorphism, APJ G212A polymorphism