Melike GEZEN, Ümit YILMAZ, Osman FAZLIOĞULLARI, Nesibe YİLMAZ, cem HOROZOĞLU, Arzu ERGEN, ŞAKİR ÜMİT ZEYBEK

Timozin beta-4 A/T polimorfizmi ve akut koroner sendrom riski

Amaç: Akut koroner sendrom (ACS), koroner arter kan akımının azalması sonucu miyokard iskemisinin neden olduğu klinik tabloların tamamını ifade eder. Thymosin beta-4 geni (Tβ4) hasarlı dokuların iyileşmesinde ve ACS’de kardiyomiyositlerin canlı kalmasında önemli rol oynamaktadır. Bu çalışmada ACS’li hastaların Tβ4 genindeki A/T (rs75112573) varyasyonunun tespit edilmesi ve akut koroner hastalığına olan etkilerinin belirlenmesi amaçlanmıştır. Yöntemler: Bu prospektif bir vaka kontrol çalışmasıdır. Çalışmaya ACS'li 48 hasta ve 45 sağlıklı kontrol birey dahil edildi. Genetik analiz, polimeraz zincir reaksiyonu/restriksiyon parça uzunluk polimorfizmi (PCR / RFLP) yöntemleri kullanılarak yapıldı.Bulgular: Kontrol grubu ile karşılaştırıldığında hasta grubunda AT genotipi (p<0.001, X2:12.40, OR:5.42, %95 CI:2.02-14.53) ve A alleli (p<0.001, X2:17.22, OR:6.66, %95 CI:2.61-16.98) taşıma sıklığı anlamlı olarak yükselmiştir. Kontrol grubunda ise TT genotip sıklığının hasta grubuna göre istatistiksel olarak yüksek olduğu gözlemlenmiştir (p<0.001, X2:17.22, OR:2.13, %95 CI:1.44-3.16). Hasta grubumuzun LDL-kolesterol seviyesi (p<0.001, %95 CI:30.12-55.90), kontrol grubumuzun ise HDL-kolesterol seviyesi yüksek bulunmuştur (p<0.001, %95 CI:5.30-15.34). Hasta grubunda AT genotipi taşıyanlarda AA genotipi taşıyanlara göre kolesterol ve HDL-kolestrol düzeyleri anlamlı derecede yüksek olarak bulunmuştur (p=0.036, %95 CI:0.59-17.25). VLDL-kolestreol düzeyleri ise hasta grubunda AA genotipi taşıyanlarda, AT (p=0.011, %95 CI:6.73-49.86) ve TT (p=0.018, %95 CI:4.95-49.49) genotipi taşıyanlara göre anlamlı şekilde yükselmiştir. Sonuç: Tβ4 A/T (rs75112573) gene polymorphism için AT genotipi ve A alleli taşımanın ACS riskini artırabileceği sonucuna ulaşılabilir.

Anahtar Kelimeler:

Timozin beta-4 (Tβ4) A/T, polimorfizm, akut koroner sendrom, PCR-RFLP

Thymosin beta-4 A/T polymorphism and acute coronary syndrome risk

Aim: Acute coronary syndrome (ACS) describes all the clinical conditions due to myocardial infarction that is caused by decreased blood flow in the coronary artery. Thymosin beta-4 (Tβ4) plays a significant role in the recovery of damaged tissues and promoting the survival of cardiomyocytes in ACS. In this study, it was aimed to determine the Tβ4 A/T (rs75112573) variation in ACS and its effects on the disease. Methods: This was a prospective case-control study. Forty-eight patients with ACS and 45 healthy controls were recruited for this study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).Results: The AT genotype (p<0.001, X2:12.40, OR:5.42, 95% CI:2.02-14.53) and the A allele (p<0.001, X2:17.22, OR:6.66, 95% CI:2.61-16.98) frequency was found significantly higher in the patient group, while in the control group the TT genotype was statistically higher (p<0.001, X2:17.22, OR:2.13, 95% CI:1.44-3.16). LDL-cholesterol levels in the patient group (p<0.001, 95% CI:30.12-55.90), and HDL-cholesterol levels in the control group (p<0.001, 95% CI:5.30-15.34) were significantly higher. In the patient group, total cholesterol and HDL-cholesterol levels were found significantly higher in AT genotype carriers compared to the AA genotype carriers (p=0.036, 95% CI:0.59-17.25), while VLDL-cholesterol levels were higher in the AA genotype carriers compared to the AT (p=0.011, 95% CI:6.73-49.86), and TT (p=0.018, 95% CI:4.95-49.49) genotype carriers. Conclusion: It can be concluded that carrying the Tβ4 A/T (rs75112573) gene polymorphism AT genotype and the A allele may increase risk of ACS.

Keywords:

Thymosin Beta-4 A/T, polymorphism, acute coronary syndrome, PCR-RFLP,

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1.Moodie DS. The Global Burden of Cardiovascular Disease. Congenit Heart Dis. 2016; 11:213.
2.American College of Cardiology/American Heart Association Task Force on Practice G. ACC/AHA guidelines for the management of patients with unstable angina and non-ST segment elevation myocardial infarction: executive summary and recommendations. Catheter Cardiovasc Interv. 2000; 51:505-21.
3.Coskun A, Eren SH, Korkmaz I, Guven FMK. The epidemiological and prognostic importance of the aVR lead among patients with and without ST segment elevation. Turk Gogus Kalp Damar Cerrahisi Dergisi-Turkish J Thorac Cardiovasc Surg. 2011;19:570-5.
4.Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KA, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2003;24:28-66.
5.Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc. 2009;84:917-38.
6.Smith JN, Negrelli JM, Manek MB, Hawes EM, Viera AJ. Diagnosis and management of acute coronary syndrome: an evidence-based update. J Am Board Fam Med. 2015;28:283-93.
7.Shrivastava S, Srivastava D, Olson EN, DiMaio JM, Bock-Marquette I. Thymosin beta4 and cardiac repair. Ann N Y Acad Sci. 2010;1194:87-96.
8.Goldstein AL, Hannappel E, Kleinman HK. Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. Trends Mol Med. 2005;11:421-9.
9.Yesilay AB, Karakurt O, Akdemir R, Erden G, Kilic H, Acikel S, et al. Thymosin beta4 levels after successful primary percutaneous coronary intervention for acute myocardial infarction. Turk Kardiyol Dern Ars. 2011;39:654-60.
10.Sosne G, Qiu P, Kurpakus-Wheater M. Thymosin beta 4: A novel corneal wound healing and anti-inflammatory agent. Clin Ophthalmol. 2007;1:201-7.
11.Bock-Marquette I, Saxena A, White MD, Dimaio JM, Srivastava D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature. 2004;432:466-72.
12.Crockford D. Development of thymosin beta4 for treatment of patients with ischemic heart disease. Ann N Y Acad Sci. 2007;1112:385-95.
13.Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
14.Kilic S, Simsek E, Soner Kemal H, Yuce EI, Turkoglu C, Kayikcioglu M. The role of specialized prevention clinics for the short term follow-up of acute coronary syndromes. Turk Kardiyol Dern Ars. 2017;45:498-505.
15.Ozkan AA. [Acute coronary syndromes: epidemiology]. Turk Kardiyol Dern Ars. 2013;41:1-3.
16.Achar SA, Kundu S, Norcross WA. Diagnosis of acute coronary syndrome. Am Fam Physician. 2005;72:119-26.
17.Marks ED, Kumar A. Thymosin beta4: Roles in Development, Repair, and Engineering of the Cardiovascular System. Vitam Horm. 2016;102:227-49.
18.Pipes GT, Yang J. Cardioprotection by Thymosin Beta 4. Vitam Horm. 2016;102:209-26.
19.Srivastava D, Saxena A, Michael Dimaio J, Bock-Marquette I. Thymosin beta4 is cardioprotective after myocardial infarction. Ann N Y Acad Sci. 2007;1112:161-70.
20.Bock-Marquette I, Shrivastava S, Pipes GC, Thatcher JE, Blystone A, Shelton JM, et al. Thymosin beta4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. J Mol Cell Cardiol. 2009;46:728-38.
21.Smart N, Bollini S, Dube KN, Vieira JM, Zhou B, Davidson S, et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature. 2011;474:640-4.
22.Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995;91:2844-50.