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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | 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 | 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 | 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 | the subjects were characterized by the normal coronary artery and high blood pressure |
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| 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 |
| 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 |
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Inclusion Criteria:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hussam Eddin Mohammed Shibli, PhD | Damascus university, ASPU Al-Sham Private University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Damascus University- Faculty of Pharmacy- Research and Graduate Studies Laboratory | Damascus | 011 | Syria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30755060 | Background | 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. | |
| 27825851 | Background | 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. |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| before angiography |
| 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 |
| 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 |
| 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 |
| 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 |
| 23226564 | Background | 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. |
| 22109355 | Background | 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. |
| 27073592 | Background | 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. |
| 27338090 | Background | 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. |
| 29883719 | Background | 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. |
| 33838166 | Background | 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. |
| 42207182 | Derived | Abd-Alkareem MH, Mohammed Shibli HE, Alquobaili FA. Reduced plasma APJ levels and APLNR G212A polymorphism in Syrian patients with coronary artery disease. Curr Med Res Opin. 2026 Mar;42(3):439-449. doi: 10.1080/03007995.2026.2668774. Epub 2026 May 28. |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |