Matrix metalloproteinase-2 and angiotensin-1 gene polymorphisms in patient who have coronary artery disease

Year 2022, , 29 - 36, 01.01.2022

Kadri Gökçe Ramazan Sabırlı , Aylin Köseler , İbrahim Türkçüer , Atakan Yılmaz

https://doi.org/10.31362/patd.886194

Abstract

Introduction: The rupture of atherosclerotic plaques is caused by the impact of matrix metalloproteinases (MMPs) upon the local fibrous valve and so might convert a chronic disease to a myocardial infarction, ultimately leading to instant death. Angiotensin converting enzyme (ACE) is actively engaged in the pathogenesis of ischemic heart disease. This study tries to unravel whether/how ACE and MMP-2 gene polymorphism contributes to the occurrence of Coronary Artery Disease (CAD).
Materials and methods: A total of 300 individuals (100 healthy/200 patients) were included in the study. A PCR-RFLP method was utilized for ACE gene I/D and DNA sequencing MMP-2 (-1306 C/T) polymorphisms.
Results: The ACE-1 gene D/D, I/D and I/I genotype frequency of the CAD cohort was 50%, 29%, and 21%, respectively whereas that of the healthy control cohort was 37%, 45% and 18%, respectively. Our findings indicate that the groups differed significantly in relation to the ACE-1 genotypes (p=0.021). The frequencies of ACE-1 gene allele I and D in both cohorts did not reveal a significant difference (p=0.314). In addition, the two groups did not manifest MMP-2 (rs243865) gene polymorphism.
Conclusion: The association between MMP-2 gene polymorphism and CAD is too weak to suggest a conclusive evidence. The I/D genotype frequency remained higher in the healthy individuals than in the CAD cohort, while in the CAD group D/D genotype was more frequently than control group. Finally, the patients with D/D genotype tend to bear greater risk for cardiovascular diseases.

Keywords

MMP-2 gene polymorphism, ACE-1 gene polymorphism, coronary artery disease, Turkish population

Project Number

2018TIPF027

Koroner arter hastalığı olan hastalarda matriks metalloproteinaz-2 ve anjiyotensin-1 gen polimorfizmleri

Abstract

Giriş: MMP'lerin lokal fibröz kapak üzerindeki etkisi aterosklerotik plakların kopmasına yol açar ve sonuç olarak kronik bir hastalığı akut miyokard enfarktüsüne çevirerek ani ölüme sebep olabilir. ACE (Anjiotensin dönüştürücü enzim)'nin çeşitli biyolojik eylemleri iskemik kalp hastalığının patogenezinde yer alır. Bu nedenle biz de çalışmamızda anjiotensin converting enzim (ACE) ve matrix metalloproteinaz 2 (MMP-2) gen polimorfizminin KAH gelişimindeki rolünü değerlendirmeyi amaçladık.
Gereç ve yöntem: Çalışmaya toplamda 300 gönüllü(100 sağlıklı/200 hasta) dahil edildi. ACE gen I/D için PCR-RFLP yöntemi ve MMP-2 (-1306 C/T) polimorfizmi için DNA dizi analizi yöntemi uygulandı.
Bulgular: Gruplar arasında ACE-1 genotiplerine bakıldığında CAD grubunda D/D genotip frekansı %50, I/D genotip frekansı %29, I/I genotip frekansı %21; kontrol grubunda D/D genotip frekansı %37, I/D genotip frekansı %45, I/I genotip frekansı %18 olarak saptanmıştır. Gruplar arasında ACE-1 geni genotipi açısından anlamlı fark mevcuttur (p=0,021). CAD grubunda ise D/D genotip frekansı kontrol grubuna göre daha yüksektir. ACE-1 geni alleli sayılarına bakıldığında her iki gruptaki I ve D allel frekansları benzerdir ve istatistiksel olarak anlanmlı fark mevcut değildir (p=0,314).
Sonuç: Bu çalışma MMP-2 (rs243865) gen polimoforfizmi ile koroner arter hastalığı arasında bir ilişki olmadığını göstermiştir. I/D genotip frekansı kontrol grubunda KAH grubuna göre daha yüksek, D/D genotip frekansı ise KAH grubunda kontrol grubuna göre daha yüksekti. D/D genotipli hastalarda KAH hastalığı riski artmıştır.

Keywords

ACE-1 gen polimorfizmi, MMP-2 (rs243865) gen polimorfizmi, Türk populasyonu, Koroner arter hastalığı

Supporting Institution

Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2018TIPF027

References

• 1. Vasků A, Goldbergová M, Izakovicová Hollá L, et al. A haplotype constituted of four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) is associated with coronary triple-vessel disease. Matrix Biol 2004;22:585-591. https://doi.org/10.1016/j.matbio.2003.10.004.
• 2. Alp E, Menevse S, Tulmac M, et al. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction. Genet Test Mol Biomarkers 2011;15:193-202. https://doi.org/10.1089/gtmb.2010.0113.
• 3. Delgado-Enciso I, Gonzalez-Hernandez NA, Baltazar-Rodriguez LM, et al. Association of matrix metalloproteinase-2 gene promoter polymorphism with myocardial infarction susceptibility in a Mexican population. J Genet 2009;88:249-252. https://doi.org/10.1007/s12041-009-0035-9.
• 4. Dhillon OS, Khan SQ, Narayan HK, et al. Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome. Clin Sci (Lond) 2009;118:249-257. https://doi.org/10.1042/CS20090226.
• 5. Pérez-Hernández N, Vargas-Alarcón G, Martínez-Rodríguez N, et al. The matrix metalloproteinase 2-1575 gene polymorphism is associated with the risk of developing myocardial infarction in Mexican patients. J Atheroscler Thromb 2012;19:718-727. https://doi.org/10.5551/jat.11817.
• 6. Bostan C, Karcıer S. Angiotensin converting enzymn gene polimorphism and cardiovascular diseases. Türk Kardiyol Dern Arş 2002;30:441-448.
• 7. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000;20:484-492. https://doi.org/10.1161/01.atv.20.2.484.
• 8. Lindpaintner K, Pfeffer MA, Kreutz R, et al. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995;332:706-711. https://doi.org/10.1056/NEJM199503163321103.
• 9. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641-644. https://doi.org/10.1038/359641a0.
• 10. Ko YL, Ko YS, Wang SM, et al. Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese. Hum Genet 1997;100:210-214. https://doi.org/10.1007/s004390050492.
• 11. Akbulut T, Bilsel T, Uyarel H, et al. The role of angiotensin converting enzyme gene polymorphism in the development of premature coronary artery disease. Türk Kardiyol Dern Arş 2004;32:23-27.
• 12. Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342:145-153. https://doi.org/10.1056/NEJM200001203420301.
• 13. Nakahara K, Matsushita S, Matsuoka H, et al. Insertion/deletion polymorphism in the angiotensin-converting enzyme gene affects heart weight. Circulation 2000;101:148-151. https://doi.org/10.1161/01.cir.101.2.148.
• 14. Eren Z, Kantarcı G, Kurt T, et al. Association of Angiotensin Converting Enzyme Polymorphism and the Risk of Myocardial Infarction in Turkish Patients. Türkiye Tıp Dergisi 2002;9:95-101.
• 15. Pfohl M, Koch M, Prescod S, et al. Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study. Eur Heart J 1999;20:1318-1325. https://doi.org/10.1053/euhj.1999.1543.
• 16. Nakai K, Itoh C, Miura Y, et al. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation 1994;90:2199-2202. https://doi.org/10.1161/01.cir.90.5.2199.
• 17. Peterlin B, Petrovic D, Zorc M, et al. Deletion/insertion polymorphism in the angiotension-converting enzyme gene as a risk factor in the Slovenian patients with coronary heart disease. Pflugers Arch 2000;439:40-41. https://doi.org/10.1007/s004240000084.
• 18. Tokunaga S, Tsuji H, Nishiue T, et al. Lower mortality in patients with the DD genotype of the angiotensin-converting enzyme gene after acute myocardial infarction. Acta Cardiol 2001;56:351-355. https://doi.org/10.2143/AC.56.6.2005698.
• 19. Tokgözoğlu SL, Alikaşifoğlu M, Unsal, et al. Angiotensin converting enzyme gene polymorphism and the risk and extent of ischemic heart disease among Turkish patients. Coron Artery Dis 1997;8:137-141. https://doi.org/10.1136/hrt.81.5.518.
• 20. Fujisawa T, Ikegami H, Shen GQ, et al. Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM. Diabetes Care 1995;18:983-985. https://doi.org/10.2337/diacare.18.7.983.
• 21. Rigat B, Hubert C, Corvol P, et al. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992;20:1433. https://doi.org/10.1093/nar/20.6.1433-a.
• 22. Gonzalez-Hernandez NA, Millan-Guerrero RO, Ceja-Espiritu G, et al. A polymorphism in the matrix metalloproteinase-2 (MMP-2 -1306T>C) gene promoter is associated with high risk of ischemic stroke in hypertensive patients. Genes Genom 2008;30:533-540.
• 23. Bhatti GK, Bhatti JS, Vijayvergiya R, et al. Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians. Indian J Clin Biochem 2017;32:163-170. https://doi.org/10.1007/s12291-016-0588-3.
• 24. Amara A, Mrad M, Sayeh A, et al. The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on Coronary Artery Disease. Clin Appl Thromb Hemost 2018;24:157-163. https://doi.org/10.1177/1076029617744320.
• 25. Gupta S, Agrawal BK, Goel RK, et al. Angiotensin-converting enzyme gene polymorphism in hypertensive rural population of Haryana, India. J Emerg Trauma Shock 2009;2:150-154. https://doi.org/10.4103/0974-2700.55323.
• 26. Borah PK, Shankarishan P, Hazarika NC, et al. Hypertension subtypes and angiotensin converting enzyme (ACE) gene polymorphism in Indian population. J Assoc Physicians India 2012;60:11,15-17.
• 27. Ghaderian SM, Akbarzadeh Najar R, Tabatabaei Panah AS. Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction. Coron Artery Dis 2010;21:330-335. https://doi.org/10.1097/MCA.0b013e32833ce065.
• 28. Alp E, Menevse S, Tulmac M, et al. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction. Genet Test Mol Biomarkers 2011;15:193-202. https://doi.org/10.1089/gtmb.2010.0113.