Determination of the adrenomedullin gene variations in patients with coronary artery disease: Evaluation of the ADM gene in coronary artery disease

Esra Çolak Geniş; Muhammet Burak Batır; Hamide Betül Gerik-Çelebi; Fethi Sırrı Çam

doi:10.28982/josam.7950

Authors

Esra Çolak Geniş Department of Medical Genetics, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey https://orcid.org/0000-0003-4222-0530
Muhammet Burak Batır Department of Medical Genetics, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey https://orcid.org/0000-0002-8722-5055
Hamide Betül Gerik-Çelebi Department of Medical Genetics, Balikesir Atatürk City Hospital, Balikesir, Turkey https://orcid.org/0000-0001-5218-7880
Fethi Sırrı Çam Department of Medical Genetics, Faculty of Medicine, Manisa Celal Bayar University, Manisa, Turkey https://orcid.org/0000-0002-0972-8896

DOI:

https://doi.org/10.28982/josam.7950

Keywords:

Coronary artery disease, Atherosclerosis, Vasodilation, ADM gene

Abstract

Background/Aim: Coronary artery disease is characterized by atherosclerosis in the vessel wall. The protein encoded by the adrenomedullin (ADM; OMIM No. 103275) gene is a preprohormone, post-translationally modified to form two biologically active peptides. These peptides are involved in a myriad of functions including vasodilation, bronchodilation, regulation of hormone secretion, growth modulation, promotion of angiogenesis, and antimicrobial activity. This study was designed to explore the correlation between the development of atherosclerosis and variations in the ADM gene.

Methods: The study analyzed 62 cases with atheromatous plaques and 46 cases without such plaques. Genomic DNA was extracted from peripheral blood. Variations in the ADM gene were determined by Sanger sequencing.

Results: In this study, four different variants were found in the ADM gene, including c.-2140T>C (rs3814700), c.248+91T>G (rs545190978), c.150C>G (rs5005), and c.261C>T (rs767028428 C>T). The allele frequencies of these ADM gene polymorphisms in patients were as follows: T at 93% and C at 7% for rs3814700 (T>C); T at 99.2% and G at 0.08% for rs545190978 (T>G); C at 99.2% and G at 0.08% for rs5005 (C>G); and C at 99.2% and T at 0.08% for rs767028428 (C>T).

Conclusion: It was found that there was no significant difference in allele frequencies and genotypes of these polymorphic regions between the patients and the control group.

Downloads

Download data is not yet available.

References

Mallika V, Goswami B, Rajappa M. Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology. 2007;58(5):513-22. doi: 10.1177/0003319707303443.

Tousoulis D, Kampoli AM, Papageorgiou N, Androulakis E, Antoniades C, Toutouzas K, et al. Pathophysiology of atherosclerosis: the role of inflammation. Curr Pharm Des. 2011;17(37):4089-110. doi: 10.2174/138161211798764843.

Wong HK, Cheung TT, Cheung BM. Adrenomedullin and cardiovascular diseases. JRSM Cardiovasc Dis. 2012;1(5):cvd.2012.012003. doi: 10.1258/cvd.2012.012003.

Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21(2):138-67. doi: 10.1210/edrv.21.2.0396.

Bunton DC, Petrie MC, Hillier C, Johnston F, McMurray JJ. The clinical relevance of adrenomedullin: a promising profile? Pharmacol Ther. 2004;103(3):179-201. doi: 10.1016/j.pharmthera.2004.07.002.

Nakayama M, Takahashi K, Kitamuro T, Murakami O, Shirato K, Shibahara S. Transcriptional control of adrenomedullin induction by phorbol ester in human monocytic leukemia cells. Eur J Biochem. 2000;267(12):3559-66. doi: 10.1046/j.1432-1327.2000.01384.x.

Hosomi N, Ohyama H, Takahashi T, Shinomiya K, Naya T, Ban CR, et al. Plasma adrenomedullin and carotid atherosclerosis in atherothrombotic ischemic stroke. J Hypertens. 2004;22(10):1945-51. doi: 10.1097/00004872-200410000-00017.

Schnabel RB, Wild PS, Wilde S, Ojeda FM, Schulz A, Zeller T, et al. Multiple biomarkers and atrial fibrillation in the general population. PLoS One. 2014;9(11):e112486. doi: 10.1371/journal.pone.0112486.

Ong KL, Tso AW, Leung RY, Cherny SS, Sham PC, Lam TH, et al. A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese. Clin Chim Acta. 2011;412(3-4):353-7. doi: 10.1016/j.cca.2010.11.007.

Cheung BM, Ong KL, Tso AW, et al. Investigators of Hong Kong Cardiovascular Risk Factor Prevalence Study. Plasma adrenomedullin level is related to a single nucleotide polymorphism in the adrenomedullin gene. Eur J Endocrinol. 2011;165(4):571-7. doi: 10.1530/EJE-11-0513.

Primer3Plus, Online software primer design program http://www.bioinformatics.nl/cgi-bin/primer3plus/primer3plus.cgi

Mörtberg J, Salzinger B, Lundwall K, et al. Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function. Int J Cardiol. 2023;373:64-71. doi: 10.1016/j.ijcard.2022.12.005.

Mahendra J, Srinivasan S, Kanakamedala A, D N, Namasivayam A, Mahendra L, et al. Expression of trefoil factor 2 and 3 and adrenomedullin in chronic periodontitis subjects with coronary heart disease. J Periodontol. 2023;94(5):694-703. doi: 10.1002/JPER.22-0467.

Li Y, Staessen JA, Li LH, Gao PJ, Thijs L, Brand E, et al. Blood pressure and urinary sodium excretion in relation to the A-1984G adrenomedullin polymorphism in a Chinese population. Kidney Int. 2006;69(7):1153-8. doi: 10.1038/sj.ki.5000213.

Chang CL, Cai Z, Hsu SYT. Stable adrenomedullin analog mitigates placental ischemia-induced hypertension and fetal growth restriction in rats. J Hypertens. 2023;41(7):1127-41. doi: 10.1097/HJH.0000000000003440.

An R, Xi C, Xu J, Liu Y, Zhang S, Wang Y, et al. Intramyocardial Injection of Recombinant Adeno-Associated Viral Vector Coexpressing PR39/Adrenomedullin Enhances Angiogenesis and Reduces Apoptosis in a Rat Myocardial Infarction Model. Oxid Med Cell Longev. 2017;2017:1271670. doi: 10.1155/2017/1271670.