The Investigation Of Relationship Between Atrial Fibrillation And ACE Gene Polymorphism.

Öz

Objective: Atrial fibrillation (AF) is the most common cardiovascular arrhythmia. It has been suggested that the renin-angiotensin system (RAS) has an important role in the pathophysiology of AF. Studies have shown that there is a relationship between ACE gene polymorphism and AF. In this study, we examined the relationship between ACE gene polymorphism and AF in our population. Materials and Methods: We have examined this polymorphism in 97 patients and 83 controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism were used to analyse gene polymorphisms. Results: ACE II, ID and DD genotype distributions in the patient and control groups, respectively, were II: 17.5%, ID: 42.3%, DD: 40.2%; II: 27.7%, ID: 48.2%, DD: 24.1%. ACE I and D allele frequencies were determined as I: 0.386, D: 0.614 in the patient group, while I: 0.518, D: 0.482 in the control group, and a significant correlation was found between the patient and control groups (X2 = 5.98 and p=0.050). Conclusion: In this study, we found that the polymorphisms of ACE I/D gene polymorphism was associated with AF in our population.

Anahtar Kelimeler

• Atrial fibrillation
• ACE
• gene
• polymorphism.

Atrial Fibrilasyon İle ACE Gen Polimorfizmi Arasındaki İlişkinin İncelenmesi

Öz

Giriş ve Amaç: Atriyal fibrilasyon (AF) kardiyovasküler kaynaklı ritim bozuklukları içinde en sık görülenidir. Renin angiotensin sistemi (RAS)’nin AF patofizyolojisinde önemli bir role sahip olduğu ileri sürülmektedir. Yapılan çalışmalarda, ACE gen polimorfizmi ile AF arasında bir ilişki olduğu belirtilmiştir. Bu çalışmada, bizim toplumumuzda ACE gen polimorfizmi ile AF arasındaki ilişkiyi inceledik. Gereç ve Yöntemler: Bu polimorfizmin analizi 97 hasta ve 83 sağlıklı kontrolde gerçekleştirildi. Bu analiz için Polimeraz zincir reaksiyonu ve kısıtlayıcı enzim kesimi kullanıldı. Bulgular: Hasta ve kontrol grubunda ACE II, ID ve DD genotip dağılımları sırasıyla, II: % 17.5, ID: %42.3, DD: %40.2; II: % 27.7, ID: % 48.2, DD: %24.1 olarak bulunmuştur. ACE I ve D alel frekansları ise hasta grubunda I: 0.386, D: 0.614 iken kontrol grubunda I: 0.518, D: 0.482 olarak tespit edilmiş olup hasta ve kontrol grupları arasında anlamlı bir ilişki olduğu saptanmıştır (X2 = 5.98 ve p=0.050). Sonuç: Bu çalışmada, bizim toplumumuzda, ACE genindeki I/D polimorfizmi ile AF arasında istatiksel olarak anlamlı bir ilişki olduğu saptanmıştır

Anahtar Kelimeler

• Atriyal fibrilasyon
• ACE
• gen
• polimorfizm

Kaynakça

1. 1-) Özyurtlu, F. , Çetin, N. "Nonvalvüler Atriyal Fibrilasyon Hastalarında Dabigatran Tedavisinin Trombosit Hacim İndeksleri ve Trombosit Sayısı Üzerine Etkileri". Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 7 (2020 ): 373-376
2. 2-) Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: The Framingham Study. Stroke 1991; 22:983–988.
3. 3-) Krahn AD, Manfreda J, Tate RB, Mathewson FA, Cuddy TE. The natural history of atrial fibrillation: Incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med 1995; 98:476–484.
4. 4-) Wachtell K, Hornestam B, Lehto M, et al. Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) Study. J Am Coll Cardiol 2005; 45:705–711.
5. 5-) Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982;306:1018–22.
6. 6-) Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham heart study. JAMA 1994;271:840–4.
7. 7-) Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F; “An insertion/deletion polymorphism in the angiotensin-1-converting enzyme gene accounting for half the variance of serum enzyme levels”. J Clin Invest, 86; 1343-1346, 1990.
8. 8-) Danser AHJ, Schalekamp MADH, Bax VA, van den Brink AM, Saxena PR, ReiggerGAJ, et al; “Angiotensin converting enzyme in the human heart : effect of the deletion/insertion polymorphism. Circulation, 92: 1387-1388, 1995.

9. 9-) Gharavi AG, Lipkowitz MB, Diamond JA, Jhang JS, Phillips RA. Deletion polymorphism of the angiotensin-converting enzyme gene is independently associated with left ventricular mass and geometric remodelling in systemic hypertension. Am J Cardiol 1996;77:1315–9.
10. 10-) Schut AF, Bleumink GS, Stricker BH, et al. Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects. Eur Heart J 2004;25:2143–8.
11. 11-) Fatini C, Abbate R, Pepe G, et al. Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms. Eur Heart J 2000;21:633–8.
12. 12-) Ogimoto A, Hamada M, Nakura J, Miki T, Hiwada K. Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy. J Hum Genet 2002;47:184–9.
13. 13-) Goette A, Staack T, Rocken C, et al. Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 2000;35: 1669–77.
14. 14-) Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion / deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 20:1433. (1992)
15. 15-) Shanmugam V, Sell KW, Saha BK (1993) Mistyping ACE heterozygotes. PCR Methods Appl 3:120–121.
16. 16-) Kem DC, Brown RD. Renin--from beginning to end. N Engl J Med. 1990 Oct 18;323(16):1136-7.
17. 17-) Beldent V, Michaud A, Wei L, Chauvet MT, Corvol P. Proteolytic release of human angiotensin-converting enzyme. Localization of the cleavage site. J Biol Chem. 1993 Dec 15;268(35):26428-34
18. 18-) Zisman LS. Inhibiting tissue angiotensin-converting enzyme: a pound of flesh without the blood? Circulation. 1998 Dec 22-29;98(25):2788-90.
19. 19-) Ashizawa N, Graf K, Do YS, et al. Osteopontin is produced by rat cardiac fibroblasts and mediates AII-induced DNA synthesis and collagen gel contraction. J Clin Invest 1996;98:2218–27.
20. 20-) Rothermund L, Kreutz R, Kossmehl P, et al. Early onset of chondroitin sulphate and osteopontin expression in angiotensin II-dependent left ventricular hyperthrophy. Am J Hypertens 2002;15:644–52.
21. 21-) Yamashita T, Hayami N, Ajiki K, Oikawa N, Sezaki K, Inoue M, et al. Is ACE gene polymorphism associated with lone atrial fibrillation? Jpn Heart J. 1997 Sep;38(5):637-41. 22-) Tsai CT, Lai LP, Lin JL, et al. Renin–angiotensin system gene polymorphisms and atrial fibrillation. Circulation 2004;109:1640–6.
22. 23-) Zaman AG, Kearney MT, Schecter C, Worthley SG, Nolan J. Angiotensin converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation. Am Heart J 2004;147:823–7.
23. 24-) Ribichini F, Steffenino G, Dellavalle A, et al. Plasma activity and insertion/deletion polymorphism of angiotensin I converting enzyme: a major risk factor and a marker of risk for coronary stent restenosis. Circulation 1998;97:147–54.
24. 25-) Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. J Am Coll Cardiol 2005;45:1832–9.