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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05562687
• Other study ID #: UDFP-Chemical-02-2022
• Status: Completed
• Start date: December 15, 2019
• Est. completion date: August 18, 2022

Study information

• Verified date: May 2024
• Source: Damascus University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: August 18, 2022
• Est. primary completion date: January 5, 2022
• Gender: All
• Age group: 30 Years to 78 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Hypertension
• Myocardial Ischemia

Locations

Country	Name	City	State
Syrian Arab Republic	Damascus University- Faculty of Pharmacy- Research and Graduate Studies Laboratory	Damascus

Sponsors (1)

Lead Sponsor	Collaborator
Damascus University

Country where clinical trial is conducted

Syrian Arab Republic, 

References & Publications (8)

Akcilar R, Yumun G, Bayat Z, Donbaloglu O, Erselcan K, Ece E, Kokdasgil H, Genc O. Characterization of the apelin -1860T>C polymorphism in Turkish coronary artery disease patients and healthy individuals. Int J Physiol Pathophysiol Pharmacol. 2015 Dec 25;7(4):165-71. eCollection 2015. — View Citation

Castan-Laurell I, Dray C, Valet P. The therapeutic potentials of apelin in obesity-associated diseases. Mol Cell Endocrinol. 2021 Jun 1;529:111278. doi: 10.1016/j.mce.2021.111278. Epub 2021 Apr 7. — View Citation

Falcone C, Bozzini S, Schirinzi S, Buzzi MP, Boiocchi C, Totaro R, Bondesan M, Pelissero G. APJ polymorphisms in coronary artery disease patients with and without hypertension. Mol Med Rep. 2012 Feb;5(2):321-5. doi: 10.3892/mmr.2011.685. Epub 2011 Nov 21. — View Citation

Huang F, Zhu P, Huang Q, Yuan Y, Lin F, Li Q. Associations between gene polymorphisms of the apelin-APJ system and the risk of hypertension. Blood Press. 2016 Aug;25(4):257-62. doi: 10.3109/08037051.2016.1156905. Epub 2016 Jun 24. — View Citation

Jin W, Su X, Xu M, Liu Y, Shi J, Lu L, Niu W. Interactive association of five candidate polymorphisms in Apelin/APJ pathway with coronary artery disease among Chinese hypertensive patients. PLoS One. 2012;7(12):e51123. doi: 10.1371/journal.pone.0051123. Epub 2012 Dec 3. — View Citation

Nowzari Z, Masoumi M, Nazari-Robati M, Akbari H, Shahrokhi N, Asadikaram G. Association of polymorphisms of leptin, leptin receptor and apelin receptor genes with susceptibility to coronary artery disease and hypertension. Life Sci. 2018 Aug 15;207:166-171. doi: 10.1016/j.lfs.2018.06.007. Epub 2018 Jun 6. — View Citation

Wang T, Liu C, Jia L, Ding J. The association between apelin polymorphisms and hypertension in China: A meta-analysis. J Renin Angiotensin Aldosterone Syst. 2019 Jan-Mar;20(1):1470320319827204. doi: 10.1177/1470320319827204. — View Citation

Zhong JC, Zhang ZZ, Wang W, McKinnie SMK, Vederas JC, Oudit GY. Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases. Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):1942-1950. doi: 10.1016/j.bbadis.2016.11.007. Epub 2016 Nov 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	BMI	measurement of body weight and height will be recorded to calculate the body mass index	before angiography
Secondary	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
Secondary	Plasma levels of triglycerides (TG)	Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 3000 g for 10 min, then plasma specimens were stored at -80°C until analysis	Collecting blood samples before angiography
Secondary	total cholesterol (TC) levels in plasma	Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 3000 g for 10 min, then plasma specimens were stored at -80°C until analysis	Collecting blood samples before angiography
Secondary	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 3000 g for 10 min, then plasma specimens were stored at -80°C until analysis	Collecting blood samples before angiography
Secondary	low-density lipoprotein cholesterol (LDL-C)	Blood samples will be obtained after a 10-h overnight fast before angiography and centrifuged at 3000 g for 10 min, then plasma specimens were stored at -80°C until analysis	Collecting blood samples before angiography