Fatma Tuba AKDENİZ, Seda GÜLEÇ YILMAZ, Cemil Selim İSBİR, Yaşar BİRKAN, David Sinan ESENSOY, Gözde ÖZCAN, Atike TEKELİ KUNT, Turgay İSBİR

Sol Ventrikül Hipertrofisinde (RRM1, RRM2, ERCC2) DNA Tamir Gen Polimorfizmleri

DOI: 10.26650/experimed.2019.19024 Amaç: Sol Ventrikül Hipertrofisi (SVH) kardiak hastalıklar için sık görülen bir risk faktörüdür. Bu çalışmada DNA tamir gen polimorfizimleri ve sol ventrikül hipertrofisi arasındaki ilişkiyi araştırdık. Gereç ve Yöntem: Periferik kandan izole edilen DNA örnekleri RRM1 (rs12806698), RRM2 (rs6859180) ve ERCC2 (rs13181) genleri için Gerçek Zamanlı Polimeraz Zincir reaksiyon (GZ- PZR) ile genotiplendirildi. Bulgular: Kontrol ve hasta grupları arasında RRM2 (p=0,365) ve ERCC2 (p=0,740) genleri için önemli fark olmamasına rağmen, RRM1 (A>C) CC genotip frekansı SVH hastalarında kontrol grubuna göre anlamlı şekilde yüksek olarak bulundu (p=0,018). RRM1 geni yabani tip A allel taşıyıcıları sağlıklı kontrolde SVH li hastalara göre anlamlı şekilde yüksek olarak tespit edildi (p=0,029). Sonuç: RRM1 CC genotipi SVH’ne karşı bir risk faktörü olabilirken RRM1 AC genotipi ve A alleli koruyucu role sahip olabilir. Cite this article as: Akdeniz FT, Güleç Yılmaz S, İsbir CS, Birkan Y, Esensoy DS, Özcan G, et al. Preliminary Study: DNA Repair Gene Polymorphisms (RRM1, RRM2, ERCC2) In Left Ventricular Hypertrophy. Experimed 2019; 9(3): 99-104.

Anahtar Kelimeler:

SVH, DNA tamir genleri, polimorfizm

Preliminary Study: DNA Repair Gene Polymorphisms (RRM1, RRM2, ERCC2) In Left Ventricular Hypertrophy

DOI: 10.26650/experimed.2019.19024 Objective: Left ventricular hypertrophy (LVH) accounts for one of the most important independent risk factors for cardiac diseases. In the present study, we investigate the relationship of DNA repair gene polymorphisms and LVH. Material and Method: DNA samples isolated from peripheral blood were genotyped with real-time polymerase chain reaction (RT-PCR) for RRM1 (rs12806698), RRM2 (rs6859180) and ERCC2 (rs13181) genes. Results: Although there were no significant differences for RRM2 (p=0.365) and ERCC2 (p=0.740) genes. RRM1 (A>C) CC genotype was significantly higher in the LVH than control groups (p=0.018). RRM1gene wild type A allele carriers were significantly higher in the healthy controls than the LVH group (p=0.029). Conclusion: RRM1 gene CC genotype could be a risk factor, whereas the RRM1 gene AC genotype and the A allele might play a protective role against LVH. Cite this article as: Akdeniz FT, Güleç Yılmaz S, İsbir CS, Birkan Y, Esensoy DS, Özcan G, et al. Preliminary Study: DNA Repair Gene Polymorphisms (RRM1, RRM2, ERCC2) In Left Ventricular Hypertrophy. Experimed 2019; 9(3): 99-104.

Keywords:

LVH, DNA repair genes, polymorphism,

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1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017; 135: 146-603. [CrossRef] 2. Messerli FH, Schmieder R. Left ventricular hypertrophy. A cardiovascular risk factor in essential hypertension. Drugs 1986; 31: 192-201. [CrossRef] 3. Davidson, BP, Giraud GD. Left ventricular function and the systemic arterial vasculature: remembering what we have learned. J Am Soc Echocardiogr 2012; 25: 891-94. [CrossRef] 4. Pokharel P, Bella JN. Regression of left ventricular hypertrophy: Lessons from clinical trials. OA Evidence-Based Medicine 2013; 1: 13. https://doi.org/10.13172/2053-2636-1-2-1110. [CrossRef] 5. Elledge SJ, Zhou Z, Allen JB. Ribonucleotide reductase: regulation, regulation, regulation. Trends Biochem Sci 1992; 17: 119-23. [CrossRef] 6. Oh IJ, Ban HJ, Kim KS, Song SY, Na KJ, Kim YH, et al. Response to gemcitabine-platinum chemotherapy by single nucleotide polymorphisms of RRM1 and ERCC1 genes in patients with non-small-cell lung cancer. Thorac Cancer 2012; 3: 19-26. [CrossRef] 7. Thomson KS, Odom GL, Murry CE, Mahairas GG, Moussavi-Harami F, Teichman SL, et al. Translation of Cardiac Myosin Activation with 2-deoxy-ATP to Treat Heart Failure via an Experimental Ribonucleotide Reductase-Based Gene Therapy. JACC Basic Transl Sci 2016; 1: 666-79. [CrossRef] 8. Korte FS, Dai J, Buckley K, Feest ER, AdamekN, Geeves MA, et al. Upregulation of cardiomyocyte ribonucleotide reductase increases intracellular 2 deoxy-ATP, contractility, and relaxation. J Mol Cell Cardiol 2011; 51: 894-901. [CrossRef] 9. Nowakowski SG, Kolwicz SC, Korte FS, Luo Z, Robinson-Hamm JN, Page JL, et al. Transgenic overexpression of ribonucleotide reductase improves cardiac performance. Proc Natl Acad Sci U S A 2013; 110: 6187-92. [CrossRef] 10. Kadota S, Carey J, Reinecke H, Leggett J, Teichman S, Laflamme MA, et al. Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure. Eur J Heart Fail 2015; 17: 772-81. [CrossRef] 11. Cervelli T, Borghini A, Galli A, Andreassi MG. DNA damage and repair in atherosclerosis: current insights and future perspectives. Int J Mol Sci 2012; 13:16929-44. [CrossRef] 12. Gallaugher LD, Henry JC, Kearns PN, Elford HL, Bergdall VK, Cardaunel AJ. Ribonucleotide reductase inhibitors reduce atherosclerosis in a double-injury rabbit model. Comp Med 2009; 59: 567-72. 13. Nowsheen S, Yang ES. The Intersection Between Dna Damage Response And Cell Death Pathways. Exp Oncol 2012; 34: 243-54. 14. Choi YH, Cowan DB, Moran AM, Colan SD, Stamm C, Takeuchi K, et al. Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium. J Thorac Cardiovasc Surg 2009; 137: 1356-62. [CrossRef] 15. Bepler G, Zheng Z, Gautam A, Sharma S, Cantor A, Sharma A, et al. Ribonucleotide reductase M1 gene promoter activity, polymorphisms, population frequencies, and clinical relevance. Lung Cancer 2005; 47: 183-92. [CrossRef] 16. Garavaglia GE, Messerli FH, Schmieder RE, Nunez BD, Oren S. Sex differences in cardiac adaptation to essential hypertension. Eur Heart J 1989; 10: 1110-4. [CrossRef] 17. Gradman AH, Alfayoumi F. From Left Ventricular Hypertrophy to Congestive Heart Failure: Management of Hypertensive Heart Disease. Prog Cardiovasc Dis 2006; 48: 326-34. [CrossRef]