Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi

Melissa Tatlıdil Akal; Burak Önal; Deniz Özen; Bülent Demir; Ahmet Gökhan Akkan; Sibel Özyazgan

Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi

Abstract

ÖZET Amaç: Tipik anjinaya sahip, invaziv olmayan testlerde iskemi bulgusuna rastlanan ve koroner anjiyografide normal epikardiyal koroner arterlere sahip olan hasta popülasyonu Kardiyak Sendrom X (KSX) olarak tanımlanmaktadır. KSX hastalarında CRP ve diğer inflamatuvar belirteçlerin düzeylerinin artması, hastalığın inflamasyon aracılı bir patogeneze sahip olduğunu gösterir niteliktedir. Sitokrom P450 enzimi olan CYP2J2, koroner arter endoteli, düz kas hücreleri ve kardiyomiyositlerde yüksek düzeylerde eksprese edilen bir hem protein ailesi üyesidir. CYP2J2’nin başlıca görevi, araşidonik asidin; 5,6- 8,9- 11,12- 14,15- olmak üzere 4 farklı çeşit epoksieikozatrienoik asitlere (EET) dönüşümünü sağlamaktır. Bu EET’ler, TNF-α ile uyarılan VCAM-1’in, endotelyal ekspresyonunu azaltarak inflamatuvar yanıt oluşumunu baskılamakta ve NF-κB’yi de inhibe ederek vasküler duvara lökosit adezyonunu azaltmaktadır. CYP2J2 geni -76G>T polimorfizmi, hücre içerisinde CYP2J2 ve metabolitlerinin ekspresyonunda düşüşe neden olmaktadır. Biz bu çalışmamızda, patofizyolojisinde inflamatuvar süreçlerin etkili olduğu düşünülen KSX hastalığı ile inflamatuvar yolakta rol aldığı bilinen CYP2J2 geni -76G>T polimorfizmi arasındaki bağlantıyı incelemeyi amaçladık. Materyal ve Metot: Ardışık 125 KSX hastası ve 125 sağlıklı bireyden oluşan kontrol grubunu, CYP2J2 geni -76G>T polimorfizmi açısından karşılaştırdık. DNA örneklerinden CYP2J2 geni -76G>T polimorfizminin genotiplemesi gerçek zamanlı PCR metodu kullanılarak yapılmıştır. Bulgular: Hasta ve kontrol gruplarında görülen TT, GT ve GG genotipleri incelendiğinde, istatistiksel olarak anlamlı bir fark gözlenmemiştir (p>0,05). Sonuç: Bu durum KSX hastalığının patogenezinde, inflamasyon artışına neden olan CYP2J2 geni -76G>T polimorfizminin önemli bir rolü olmadığını düşündürmektedir.

Keywords

kardiyak sendrom X; inflamasyon; CYP2J2; polimorfizm; mikrovasküler disfonksiyon

References

1. Egashira, K., T. Inou, Y. Hirooka, A. Yamada, Y. Urabe, and A. Takeshita, Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris andnormal coronary angiograms. N Engl J Med, 1993. 328(23): p. 1659-64.
2. Quyyumi, A.A., R.O. Cannon, 3rd, J.A. Panza, J.G. Diodati, and S.E. Epstein, Endothelial dysfunction in patients with chest pain and normal coronary arteries. Circulation, 1992. 86(6): p. 1864-71.
3. Vane, J.R., E.E. Anggard, and R.M. Botting, Regulatory functions of the vascular endothelium. N Engl J Med, 1990. 323(1): p. 27-36.
4. Christodoulidis, G., T.J. Vittorio, M. Fudim, S. Lerakis, and C.E. Kosmas, Inflammation in coronary artery disease. Cardiol Rev, 2014. 22(6): p. 279-88.
5. On, Y.K., R. Park, M.S. Hyon, S.K. Kim, and Y.J. Kwon, Are low total serum antioxidant status and elevated levels of C-reactive protein and monocyte chemotactic protein-1 associated with cardiac syndrome X? Circ J, 2005. 69(10): p. 1212-7.
6. Li, J.J., C.G. Zhu, J.L. Nan, J. Li, Z.C. Li, H.S. Zeng, et al., Elevated circulating inflammatory markers in female patients with cardiac syndrome X. Cytokine, 2007. 40(3): p. 172-6.
7. Dominguez-Rodriguez, A., P. Abreu-Gonzalez, P. Avanzas, M.A. Gomez, and J.C. Kaski, Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X. Atherosclerosis, 2010. 213(2): p. 637-41.
8. Demir, B., B. Onal, S. Ozyazgan, C. Kandaz, H. Uzun, G. Aciksari, et al., Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels. Angiology, 2016. 67(4): p. 355-63.

9. Pasceri, V., J.T. Willerson, and E.T. Yeh, Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 2000. 102(18): p. 2165-8.
10. Verma, S., S.H. Li, M.V. Badiwala, R.D. Weisel, P.W. Fedak, R.K. Li, et al., Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation, 2002. 105(16): p. 1890-6.
11. Maseri, A., F. Crea, J.C. Kaski, and T. Crake, Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol, 1991. 17(2): p. 499-506.
12. Legrand, V., J.M. Hodgson, E.R. Bates, F.M. Aueron, G.B. Mancini, J.S. Smith, et al., Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiograms. J Am Coll Cardiol, 1985. 6(6): p. 1245-53.
13. Arroyo-Espliguero, R. and J.C. Kaski, Microvascular dysfunction in cardiac syndrome X: the role of inflammation. CMAJ, 2006. 174(13): p. 1833.
14. Gonzalez, F.J., The molecular biology of cytochrome P450s. Pharmacol Rev, 1988. 40(4): p. 243-88.
15. Node, K., Y. Huo, X. Ruan, B. Yang, M. Spiecker, K. Ley, et al., Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science, 1999. 285(5431): p. 1276-9.
16. King, L.M., J. Ma, S. Srettabunjong, J. Graves, J.A. Bradbury, L. Li, et al., Cloning of CYP2J2 gene and identification of functional polymorphisms. Mol Pharmacol, 2002. 61(4): p. 840-52.
17. Spiecker, M., H. Darius, T. Hankeln, M. Soufi, A.M. Sattler, J.R. Schaefer, et al., Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation, 2004. 110(15): p. 2132-6.
18. Ma, J., S. Ramachandran, F.T. Fiedorek, Jr., and D.C. Zeldin, Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4. Genomics, 1998. 49(1): p. 152-5.
19. Brandon, S., Chest pain in patients with normal coronary arteriograms. Br Med J (Clin Res Ed), 1983. 287(6404): p. 1491-2.
20. Bass, C., C. Wade, D. Hand, and G. Jackson, Patients with angina with normal and near normal coronary arteries: clinical and psychosocial state 12 months after angiography. Br Med J (Clin Res Ed), 1983. 287(6404): p. 1505-8.
21. Humphries, K.H., A. Pu, M. Gao, R.G. Carere, and L. Pilote, Angina with “normal” coronary arteries: sex differences in outcomes. Am Heart J, 2008. 155(2): p. 375-81.
22. Sullivan, A.K., D.R. Holdright, C.A. Wright, J.L. Sparrow, D. Cunningham, and K.M. Fox, Chest pain in women: clinical, investigative, and prognostic features. BMJ, 1994. 308(6933): p. 883-6.
23. Parsyan, A. and L. Pilote, Cardiac syndrome X: mystery continues. Can J Cardiol, 2012. 28(2 Suppl): p. S3-6.
24. Jadhav, S.T., W.R. Ferrell, J.R. Petrie, O. Scherbakova, I.A. Greer, S.M. Cobbe, et al., Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X. Am J Cardiol, 2006. 97(12): p. 1727-31.
25. Botker, H.E., O. Frobert, N. Moller, E. Christiansen, O. Schmitz, and J.P. Bagger, Insulin resistance in cardiac syndrome X and variant angina: influence of physical capacity and circulating lipids. Am Heart J, 1997. 134(2 Pt 1): p. 229-37.
26. Botker, H.E., N. Moller, P. Ovesen, A. Mengel, O. Schmitz, H. Orskov, et al., Insulin resistance in microvascular angina (syndrome X). Lancet, 1993. 342(8864): p. 136-40.
27. Cosin-Sales, J., C. Pizzi, S. Brown, and J.C. Kaski, C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms. J Am Coll Cardiol, 2003. 41(9): p. 1468-74.
28. Arroyo-Espliguero, R., N. Mollichelli, P. Avanzas, E. Zouridakis, V.R. Newey, D.K. Nassiri, et al., Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X. Eur Heart J, 2003. 24(22): p. 2006-11.
29. Torres, J.L. and P.M. Ridker, Clinical use of high sensitivity C-reactive protein for the prediction of adverse cardiovascular events. Curr Opin Cardiol, 2003. 18(6): p. 471-8.
30. Cybulsky, M.I. and M.A. Gimbrone, Jr., Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science, 1991. 251(4995): p. 788-91.
31. Collins, T., H.J. Palmer, M.Z. Whitley, A.S. Neish, and A.J. Williams, A common theme in endothelial activation Insights from the structural analysis of the genes for E-selectin and VCAM-1. Trends Cardiovasc Med, 1993. 3(3): p. 92-7.
32. Fries, J.W., A.J. Williams, R.C. Atkins, W. Newman, M.F. Lipscomb, and T. Collins, Expression of VCAM-1 and E-selectin in an in vivo model of endothelial activation. Am J Pathol, 1993. 143(3): p. 725-37.
33. Harris, R.C., K.A. Munger, K.F. Badr, and K. Takahashi, Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites. FASEB J, 1990. 4(6): p. 1654-60.
34. Berlin, D.S., K. Sangkuhl, T.E. Klein, and R.B. Altman, PharmGKB summary: cytochrome P450, family 2, subfamily J, polypeptide 2: CYP2J2. Pharmacogenet Genomics, 2011. 21(5): p. 308-11.
35. Genvigir, F.D.V., A.M. Nishikawa, C.R. Felipe, H. TedescoSilva, Jr., N. Oliveira, A.B.C. Salazar, et al., Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients. Pharmacotherapy, 2017. 37(5): p. 535-545.
36. Ahmed, J.H.M., E.; Ali, G.Y.; Seifu, D.; Bekele, A.; Assefa, M.; Howe, R.; Fotoohi, A.; Hassan, M. and Aklillu, E., CYP2J2*7 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients. Pharmacogenetics and Pharmacogenomics, 2019.
37. Liu, P.Y., Y.H. Li, T.H. Chao, H.L. Wu, L.J. Lin, L.M. Tsai, et al., Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction. Atherosclerosis, 2007. 195(1): p. 199-206.
38. King, L.M., J.V. Gainer, G.L. David, D. Dai, J.A. Goldstein, N.J. Brown, et al., Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenet Genomics, 2005. 15(1): p. 7-13.
39. Polonikov, A.V., V.P. Ivanov, M.A. Solodilova, I.V. Khoroshaya, M.A. Kozhuhov, V.E. Ivakin, et al., A common polymorphism G-50T in cytochrome P450 2J2 gene is associated with increased risk of essential hypertension in a Russian population. Dis Markers, 2008. 24(2): p. 119-26.
40. Wu, S.N., Y. Zhang, C.O. Gardner, Q. Chen, Y. Li, G.L. Wang, et al., Evidence for association of polymorphisms in CYP2J2 and susceptibility to essential hypertension. Ann Hum Genet, 2007. 71(Pt 4): p. 519-25.
41. Alghasham, A., A. Ali, H. Ismail, M. Dowaidar, and A.A. Settin, CYP2J2 -50 G/T and ADRB2 G46A gene polymorphisms in Saudi subjects with hypertension. Genet Test Mol Biomarkers, 2012. 16(9): p. 1027-31.
42. Lee, C.R., K.E. North, M.S. Bray, D.J. Couper, G. Heiss, and D.C. Zeldin, CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the Atherosclerosis Risk in Communities (ARIC) study. Pharmacogenet Genomics, 2007. 17(5): p. 349-58.
43. Hoffmann, M.M., P. Bugert, U. Seelhorst, B. Wellnitz, B.R. Winkelmann, B.O. Boehm, et al., The -50G>T polymorphism in the promoter of the CYP2J2 gene in coronary heart disease: the Ludwigshafen Risk and Cardiovascular Health study. Clin Chem, 2007. 53(3): p. 539-40.
44. Borgel, J., D. Bulut, C. Hanefeld, H. Neubauer, A. Mugge, J.T. Epplen, et al., The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile. BMC Cardiovasc Disord, 2008. 8: p. 41.
45. Yan, H., Y. Kong, B. He, M. Huang, J. Li, J. Zheng, et al., CYP2J2 rs890293 polymorphism is associated with susceptibility to Alzheimer’s disease in the Chinese Han population. Neurosci Lett, 2015. 593: p. 56-60.
46. Zhu, Q., Z. Fu, Y. Ma, H. Yang, D. Huang, X. Xie, et al., A novel polymorphism of the CYP2J2 gene is associated with coronary artery disease in Uygur population in China. Clin Biochem, 2013. 46(12): p. 1047-1054.
47. Dreisbach, A.W., S. Japa, A. Sigel, M.B. Parenti, A.E. Hess, S.L. Srinouanprachanh, et al., The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension. Am J Hypertens, 2005. 18(10): p. 1276-81.

Details

Primary Language

Turkish

Subjects

Clinical Sciences

Journal Section

Research Article

Authors

Melissa Tatlıdil Akal This is me
Türkiye

Burak Önal This is me
Türkiye

Deniz Özen This is me
Türkiye

Bülent Demir This is me
Türkiye

Ahmet Gökhan Akkan This is me
Türkiye

Sibel Özyazgan This is me
Türkiye

Publication Date

August 1, 2019

Submission Date

May 7, 2019

Acceptance Date

July 19, 2019

Published in Issue

Year 2019 Volume: 9 Number: 2

IZ

https://izlik.org/JA37TF79XP

Cite

RIS / Bibtex

APA

Tatlıdil Akal, M., Önal, B., Özen, D., Demir, B., Akkan, A. G., & Özyazgan, S. (2019). Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi. Kafkas Journal of Medical Sciences, 9(2), 79-86. https://izlik.org/JA37TF79XP

AMA

1.Tatlıdil Akal M, Önal B, Özen D, Demir B, Akkan AG, Özyazgan S. Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi. Kafkas Journal of Medical Sciences. 2019;9(2):79-86. https://izlik.org/JA37TF79XP

Chicago

Tatlıdil Akal, Melissa, Burak Önal, Deniz Özen, Bülent Demir, Ahmet Gökhan Akkan, and Sibel Özyazgan. 2019. “Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi”. Kafkas Journal of Medical Sciences 9 (2): 79-86. https://izlik.org/JA37TF79XP.

EndNote

Tatlıdil Akal M, Önal B, Özen D, Demir B, Akkan AG, Özyazgan S (August 1, 2019) Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi. Kafkas Journal of Medical Sciences 9 2 79–86.

IEEE

[1]M. Tatlıdil Akal, B. Önal, D. Özen, B. Demir, A. G. Akkan, and S. Özyazgan, “Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi”, Kafkas Journal of Medical Sciences, vol. 9, no. 2, pp. 79–86, Aug. 2019, [Online]. Available: https://izlik.org/JA37TF79XP

ISNAD

Tatlıdil Akal, Melissa - Önal, Burak - Özen, Deniz - Demir, Bülent - Akkan, Ahmet Gökhan - Özyazgan, Sibel. “Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi”. Kafkas Journal of Medical Sciences 9/2 (August 1, 2019): 79-86. https://izlik.org/JA37TF79XP.

JAMA

1.Tatlıdil Akal M, Önal B, Özen D, Demir B, Akkan AG, Özyazgan S. Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi. Kafkas Journal of Medical Sciences. 2019;9:79–86.

MLA

Tatlıdil Akal, Melissa, et al. “Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi”. Kafkas Journal of Medical Sciences, vol. 9, no. 2, Aug. 2019, pp. 79-86, https://izlik.org/JA37TF79XP.

Vancouver

1.Melissa Tatlıdil Akal, Burak Önal, Deniz Özen, Bülent Demir, Ahmet Gökhan Akkan, Sibel Özyazgan. Kardiyak Sendrom X Hastalarında CYP2J2 Polimorfizminin Belirlenmesi. Kafkas Journal of Medical Sciences [Internet]. 2019 Aug. 1;9(2):79-86. Available from: https://izlik.org/JA37TF79XP