REVIEW OF THE EPHX2 GENE AND RELATED DISEASES

Year 2022, Volume: 1 Issue: 3, 107 - 111, 19.12.2022

Kamil Duran Derya Deniz Kanan

https://doi.org/10.57221/izmirtip.1152898

Abstract

The increasing frequency of chronic diseases today; while it causes situations such as decreased quality of life and premature death in patients, it also causes an increase in the burden on the health system and society. In the study of Heart Disease and Risk Factors in Turkish Adults (TEKHARF), which has been going on since 1990; it has been revealed that coronary heart disease is 6 % in the 45-54 age group, 17 % in the 55-64 age group, and 28 % in the individuals aged 65 and over. Considering the age range of 45-74 years, the prevalance of coronary mortality was found to be 7.3 per thousand in men and 3.8 per thousand in women during 24 follow-up years. According to the data of the Turkish Statistical Institute, among the causes of death in 2019, circulatory system diseases ranked first with 36.8 %, tumors came in the second place with 18.4 %, and respiratory system diseases came in the third place with 12.9 %. 39.1 % of deaths due to circulatory system diseases are caused by ischemic heart disease, 22.2 % by cerebrovascular diseases, and 25.7 % by other heart diseases.
Based on these data, when the relationship of the EPHX2 gene with cardiovascular diseases, cancer, cerebrovascular diseases and other diseases is considered, studies on this gene will shed light on the mechanisms of the previously mentioned diseases, deaths and disability due to themlt is predicted that the cost of treatment may also decrease. From this point of view, it is aimed to provide a review to the literatüre by screening the EPHX2 gene and the diseases associated with this gene.

Keywords

EPHX2, Gene, Cardiovascular Diseases, Cerebrovascular Diseases, EPHX2,Gene, Cardiovascular Diseases, Cerebrovascular Diseases

Çözünür Epoksit Hidrolaz Geni ve Bu Genle İlgili Hastalıkların Derlenmesi

Abstract

Günümüzde kronik hastalıkların sıklığının artması; hastada yaşam kalitesinin düşmesi, erken ölümlerin görülmesi gibi durumlara sebep olurken aynı zamanda sağlık sistemi ve topluma olan yükün artmasına yol açmaktadır. Bin dokuz yüz doksan yılından beri devam eden, Türk Erişkinlerindeki Kalp Hastalığı ve Risk Faktörleri (TEKHARF) çalışmasında; koroner kalp hastalığının 45-54 yaş grubunda %6, 55-64 yaş grubunda %17 ve 65 yaş ve üzerindeki bireylerde %28 oranında olduğu ortaya konulmuş olup, 45-74 yaş aralığı ele alındığında, 24 takip yılı boyunca koroner mortalite prevalanslarının erkeklerde binde 7.3 ve kadınlarda binde 3.8 düzeyinde olduğu tespit edilmiştir. Türkiye İstatistik Kurumu verilerine göre 2019 yılında ölüm nedenleri arasında, %36.8 ile dolaşım sistemi hastalıkları ilk sırada yer alırken, ikinci sırada %18.4 ile tümörler, üçüncü sırada %12.9 ile solunum sistemi hastalıkları gelmektedir. Dolaşım sistemi hastalıkları kaynaklı ölümlerin %39.1’ini iskemik kalp hastalığı, %22.2’sini serebrovasküler hastalıklar, %25.7’sini diğer kalp hastalıkları oluşturmaktadır. Bu veriler ışığında, çözünebilir epoksit hidrolaz (EPHX2) geninin kardiyovasküler hastalıklar, kanser, serebrovasküler hastalıklar ve diğer hastalıklar ile olan ilişkisi düşünüldüğünde bu gen üzerinde yapılan çalışmaların, daha önce sayılan hastalıkların mekanizmalarına ışık tutacağına, onlara bağlı ölümlerin, sakat kalmaların azalabileceği aynı zamanda tedavi maliyetlerinin de düşebileceği öngörülmektedir. Buradan yola çıkarak EPHX2 geni ve bu genle ilişkilendirilen hastalıklar taranarak literatüre bir derleme kazandırılması amaçlanmıştır.

Keywords

EPHX2, Gen, Kardiyovasküler Hastalıklar, Serebrovasküler Hastalıklar

References

• 1. Gautheron J, Jéru I. The multifaceted role of epoxide hydrolases in human health and disease. Int J Mol Sci. 2020;22:13.
• 2. Harris TR, Hammock BD. Soluble epoxide hydrolase: gene structure, expression and deletion. Gene. 2013;526: 61-74.
• 3. Sarı İ, Yılmaz M, Katrancıoğlu N. Abdominal aort anevrizması ve EPHX2 geni K55r Polimorfizmi. Bozok Tıp Dergisi. 2020; 10:145-51.
• 4. Van Loo B, Kingma J, Arand M, Wubbolts MG, Janssen DB. Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis. Appl Environ Microbiol. 2006;72:2905-17.
• 5. Decker M, Adamska M, Cronin A, Di Giallonardo F, Burgener J, Marowsky A et al. EH3 (ABHD9): The first member of a new epoxide hydrolase family with high activity for fatty acid epoxides. J Lipid Res. 2012;53:2038-45.
• 6. Fretland AJ, Omiecinski CJ. Epoxide hydrolases: Biochemistry and molecular biology. Chem Biol Interact. 2000;129:41-59.
• 7. Skoda RC, Demierre A, McBride OW, Gonzalez FJ, Meyer UA. Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization. J Biol Chem. 1988;263:1549-54.
• 8. Beetham JK, Tian T, Hammock BD. cDNA cloning and expression of a soluble Epoxide Hydrolase from human liver. Arch Biochem Biophys. 1993;305:197-201.
• 9. Gill SS, Hammock BD. Distribution and properties of a mammalian soluble epoxide hydrase. Biochem Pharmacol. 1980;29:389-95.
• 10. Zhang D, Xie X, Chen Y, Hammock BD, Kong W, Zhu Y. Homocysteine upregulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo. Circ Res. 2012;110:808-17.
• 11. Ai D, Pang W, Li N, Xu M, Jones PD, Yang J et al. Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy. Proc Natl Acad Sci. 2009;106:564-9.
• 12. Harris TR, Hammock BD. Soluble epoxide hydrolase: Gene structure, expression and deletion. Gene. 2013;526:61-74.
• 13. Reisdorf WC, Xie Q, Zeng X, Xie W, Rajpal N, Hoang B et al. Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease. Plos One. 2019;14:e0215033.
• 14. Inceoglu B, Jinks SL, Schmelzer KR, Waite T, Kim IH, Hammock BD. Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. Life Sci. 2006;79:2311-9.
• 15. Napimoga MH, Rocha EP, Trindade-Da-Silva CA, Demasi APD, Martinez EF, Macedo CG et al. Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption. J Periodontal Res. 2018;53:743-9.
• 16. Klocke J, Ulu A, Wu K, Rudolph B, Dragun D, Gollasch M et al. Prophylactic inhibition of soluble epoxide hydrolase delays onset of nephritis and ameliorates kidney damage in NZB/W F1 mice. Scientific Reports. 2019;9:1-11.
• 17. Sun H, Lee P, Yan C, Gao N, Wang JM, Fan X et al. Inhibition of soluble epoxide hydrolase 2 ameliorates diabetic keratopathy and impaired wound healing in mouse. Corneas Diabetes. 2018;67:1162–72.
• 18. Elmarakby AA, Faulkner J, Al-Shabrawey M, Wang MH, Maddipati KR, Imig JD. Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes. Am J Physiol Regul Integr Comp Physiol. 2011;301:1307–17.
• 19. Manhiani M, Quigley JE, Knight SF, Tasoobshirazi S, Moore T, Brands MW et al. Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension. Am J Physiol Renal Physiol.2009;297:740-8.
• 20. Simpkins AN, Rudic RD, Roy S, Tsai HJ, Hammock BD, Imig JD. Soluble epoxide hydrolase inhibition modulates vascular remodeling. Am J Physiol Heart Circ Physiol. 2010;298:795-806.
• 21. Thomson SJ, Askari A, Bishop-Bailey D. Anti-inflammatory effects of epoxyeicosatrienoic acids. Int J Vasc Med. 2012;605101.
• 22. Scott-Van Zeeland AA, Bloss CS, Tewhey R, Bansal V, Torkamani A, Libiger O et al. Evidence for the role of EPHX2 gene variants in anorexia nervosa. Molecular psychiatry. 2014;19:724–32.
• 23. Vainio P, Gupta S, Ketola K, Mirtti T, Mpindi JP et al. Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer. Am J Pathol. 2011;178:525-36.
• 24. Liu MS, Zhao H, Xu CX, Xie PB, Wang W, Yang YY et al. Clinical significance of EPHX2 deregulation in prostate cancer. Asian Journal of Andrology. 2021;23:109-15.
• 25. Zhang Y, Zhang R, Liang F, Zhang L, Liang X. Identification of metabolism-associated prostate cancer subtypes and construction of a prognostic risk model. Frontiers in Oncology. 2020;10:598801.
• 26. Kesavan R, Frömel T, Zukunft S, Brüne B, Weigert A, Wittig I et al. The consequences of soluble epoxide hydrolase deletion on tumorigenesis and metastasis in a mouse model of breast cancer. Int J Mol Sci. 2021;22:7120.
• 27. Chen C, Li G, Liao W, Wu J, Liu L, Ma D et al. Selective inhibitors of CYP2J2 related to terfenadine exhibit strong activity against human cancers in vitro and in vivo. J Pharmacol Exp Ther. 2009;329:908-18.
• 28. Wang L, Wang Y, Su B, Yu P, He J, Meng L et al. Transcriptome-wide analysis and modelling of prognostic alternative splicing signatures in invasive breast cancer: a prospective clinical study. Scientific reports. 2020;10:16504.
• 29. Liu J, Nie S, Gao M, Jiang Y, Wan Y, Ma X et al. Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis. J Cell Physiol. 2019;234:21260-73.
• 30. Zhan K, Bai Y, Liao S, Chen H, Kuang L, Luo Q et al. Identification and validation of EPHX2 as a prognostic biomarker in hepatocellular carcinoma. Mol Med Rep. 2021;24:650.
• 31. Oni-Orisan A, Cresci S, Jones PG, Theken KN, Spertus JA, Lee CR. Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an acute coronary syndrome. Prostaglandins & other lipid mediators. 2018;138:15-22.
• 32. Burdon KP, Lehtinen AB, Langefeld CD, Carr JJ, Rich SS, Freedman BI et al. Genetic analysis of the soluble epoxide hydrolase gene, EPHX2, in subclinical cardiovascular disease in the Diabetes Heart Study. Diab Vasc Dis Res. 2008;5:128-34.
• 33. Xu Y, Ding H, Peng J, Cui G, Liu L, Cianflone C et al. Association between polymorphisms of CYP2J2 and EPHX2 genes and risk of coronary artery disease. Pharmacogenet Genomics. 2011;21:489-94.
• 34. Kullmann S, Binner P, Rackebrandt K, Huge A, Haltern G, Lankisch M et al. Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention. BMC Cardiovasc Disord. 2009;9:1-7.
• 35. Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW et al. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet. 2006;15:1640-9.
• 36. Wei Q, Doris PA, Pollizotto MV, Boerwinkle E, Jacobs DR, Jr. Siscovick DS. Sequence variation in the soluble epoxide hydrolase gene and subclinical coronary atherosclerosis: interaction with cigarette smoking. Atherosclerosis. 2007;190:26-34.
• 37. Li L, Li N, Pang W, Zhang X, Hammock BD, Ai D et al. Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis. Plos one. 2014;9:e94092.
• 38. Zhang H, Wang T, Zhang K, Liu Y, Huang F, Zhu X et al. Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. Crit. Crit Care Med. 2014;42:345-54.
• 39. Lee J, Dahl M, Grande P, Tybjaerg-Hansen A, Nordestgaard BG. Genetically reduced soluble epoxide hydrolase activity and risk of stroke and other cardiovascular disease. Stroke. 2010;41:27-33.
• 40. Zhu XL , Wang L, Wang Z, Chen SZ, Zhang WQ, Ma MM. Relationship between EPHX2 gene polymorphisms and essential hypertension in Uygur, Kazakh, and Han. Genet Mol Res. 2015;14:3474-80.
• 41. Demirdogen C, Micoogulları B, Turkanoglu Y, Ozcelik A, Adalı O. Missense genetic polymorphisms of microsomal (EPHX1) and soluble epoxide hydrolase (EPHX2) and their relation to the risk of large artery atherosclerotic ischemic stroke in a Turkish population. Neuropsychiatr Dis Treat. 2021;16:3251-65.
• 42. Ma L, Jiang Y, Kong X, Yan M, Zhao T, Zhao H et al. Synergistic effect of the MTHFR C677T and EPHX2 G860A polymorphism on the increased risk of ischemic stroke in Chinese Type 2 diabetic patients. J Diabetes Res. 2017;6216205.
• 43. Yi X, Zhang B, Wang C, Liao D, Lin J, Chi L. CYP2C8 rs17110453 and EPHX2 rs751141 two-locus interaction increases susceptibility to ischemic stroke. Gene. 2015;565:85-9.