|
Association between the Cyclooxygenase-2 Gene Polymorphism (-765G>C) and Serum Prostaglandin E2 Levels in Patients with Type 2 Diabetes
|
Rozita Hezarjaribi1 , Reza Haji Hosseini2 , Safoura Khajeniazi *3  |
1- M.Sc in Biochemistry, Department of Biochemistry, Payame Noor University (PNU), Tehran, Iran. 2- Professor in Biochemistry, Payame Noor University (PNU), Tehran, Iran. 3- Associate Professor in Clinical Biochemistry, Metabolic Disorders Research Center, Biomedical Research Institute, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. , niazie80@gmail.com |
|
|
Abstract: (4813 Views) |
Background and Objective: Cyclooxygenase-2 (COX-2) is a proinflammatory enzyme whose principal product, prostaglandin E2 (PGE2), may contribute to the development of type 2 diabetes. Genetic polymorphisms are among the factors that can influence COX-2 activity or expression. This study aimed to evaluate the association between the COX-2 gene polymorphism (-765G>C) and serum PGE2 levels in patients with type 2 diabetes.
Methods: This case-control study included 50 patients with type 2 diabetes and 50 healthy individuals attending Shahid Sayyad Shirazi Teaching Hospital in Gorgan, Iran. Serum FBS, HbA1c, and PGE2 levels were measured using ELISA kits, and the gene polymorphism was determined by ARMS-PCR.
Results: The COX-2 -765G>C polymorphism was not significantly associated with either diabetes or PGE2. PGE2 levels were higher in patients with diabetes (43.42±31.2) than in healthy controls (17.67±6.38; P<0.05). PGE2 levels were significantly higher in individuals with the CG genotype (41.15±30.99) than in those with other genotypes (P<0.05).
Conclusion: The COX-2 -765G>C polymorphism, as an inflammatory mediator-related variant, had no effect on the risk of diabetes or its complications. |
|
Keywords: Diabetes Mellitus, Type 2 [MeSH], Cyclooxygenase 2 [MeSH], Prostaglandin-E Synthases [MeSH], Glycated Hemoglobin [MeSH] Article ID: Vol28-15 |
|
|
Full-Text [PDF 999 kb]
(1057 Downloads)
| | Abstract (HTML) (14 Views)
|
|
Type of Study: Original Articles |
Subject:
Biochemistry
|
|
|
|
|
|
|
| References |
1. Abel ED, Gloyn AL, Evans-Molina C, Joseph JJ, Misra S, Pajvani UB, et al. Diabetes mellitus-Progress and opportunities in the evolving epidemic. Cell. 2024 Jul;187(15):3789-820. https://doi.org/10.1016/j.cell.2024.06.029. [ DOI] [ PubMed] 2. Kellogg AP, Cheng HT, Pop-Busui R. Cyclooxygenase-2 pathway as a potential therapeutic target in diabetic peripheral neuropathy. Curr Drug Targets. 2008 Jan;9(1):68-76. https://doi.org/10.2174/138945008783431691. [ DOI] [ PubMed] 3. Antman EM, DeMets D, Loscalzo J. Cyclooxygenase inhibition and cardiovascular risk. Circulation. 2005 Aug;112(5):759-70. https://doi.org/10.1161/circulationaha.105.568451. [ DOI] [ PubMed] 4. Kamal MV, Damerla RR, Dikhit PS, Kumar NA. Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma. J Oral Biol Craniofac Res. 2023 Sep-Oct;13(5):567-74. https://doi.org/10.1016/j.jobcr.2023.07.002. [ DOI] [ PubMed] 5. Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004 Sep;63(9):901-10. https://doi.org/10.1093/jnen/63.9.901. [ DOI] [ PubMed] 6. Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE, et al. Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol. 2002 Oct;22(10):1631-36. https://doi.org/10.1161/01.atv.0000030340.80207.c5. [ DOI] [ PubMed] 7. Szczeklik W, Sanak M, Szczeklik A. Functional effects and gender association of COX-2 gene polymorphism G-765C in bronchial asthma. J Allergy Clin Immunol. 2004 Aug;114(2):248-53. https://doi.org/10.1016/j.jaci.2004.05.030. [ DOI] [ PubMed] 8. Gao J, Kang HF, Ma XB, Tang W, Liu D, Zhao Y, et al. Functional promoter -765 G > C variant in COX-2 gene is associated with the susceptibility of breast cancer in Chinese Han women. Cancer Cell Int. 2014 May;14:38. https://doi.org/10.1186/1475-2867-14-38. [ DOI] [ PubMed] 9. Konheim YL, Wolford JK. Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians. Hum Genet. 2003 Oct;113(5):377-81. https://doi.org/10.1007/s00439-003-1000-y. [ DOI] [ PubMed] 10. Martín-Vázquez E, Cobo-Vuilleumier N, López-Noriega L, Lorenzo PI, Gauthier BR. The PTGS2/COX2-PGE2 signaling cascade in inflammation: Pro or anti? A case study with type 1 diabetes mellitus. Int J Biol Sci. 2023 Aug;19(13):4157-65. https://doi.org/10.7150/ijbs.86492. [ DOI] [ PubMed] 11. Eskandari A, Heidari R, Farokhi F, Salimi Z, Ghasemi Z. [Effect of aqueous extract from rhizome of Cynodon dactylon L. pers on renal and hepatic catalase activity and testicular histopathology in diabetic rats]. Feyz Med Sci J. 2012;16(1):9-16. [Article in Persian] [ Link] 12. Mazzola S, Lira MG, Benedetti MD, Salviati A, Ottaviani S, Malerba G, et al. COX-2 promoter region polymorphisms in multiple sclerosis: lack of association of -765G>C with disease risk. Int J Immunogenet. 2007 Apr;34(2):71-74. https://doi.org/10.1111/j.1744-313x.2007.00675.x. [ DOI] [ PubMed] 13. Cipollone F, Toniato E, Martinotti S, Fazia M, Iezzi A, Cuccurullo C, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA. 2004 May;291(18):2221-28. https://doi.org/10.1001/jama.291.18.2221. [ DOI] [ PubMed] 14. Orbe J, Beloqui O, Rodriguez JA, Belzunce MS, Roncal C, Páramo JA. Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors. Clin Chim Acta. 2006 Jun;368(1-2):138-43. https://doi.org/10.1016/j.cca.2005.12.019. [ DOI] [ PubMed] 15. Kohsaka S, Volcik KA, Folsom AR, Wu KK, Ballantyne CM, Willerson JT, et al. Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study. Atherosclerosis. 2008 Feb;196(2):926-30. https://doi.org/10.1016/j.atherosclerosis.2007.02.010. [ DOI] [ PubMed] 16. Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B. Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma. Mutat Res. 2009 Apr;663(1-2):52-59. https://doi.org/10.1016/j.mrfmmm.2009.01.007. [ DOI] [ PubMed] 17. Guo Y, Zhang X, Tan W, Miao X, Sun T, Zhao D, et al. Platelet 12-lipoxygenase Arg261Gln polymorphism: functional characterization and association with risk of esophageal squamous cell carcinoma in combination with COX-2 polymorphisms. Pharmacogenet Genomics. 2007 Mar;17(3):197-205. https://doi.org/10.1097/fpc.0b013e328010bda1. [ DOI] [ PubMed] 18. Fenske R, Weeks A, Brill A, Nall R, Pabitch S, Punt M, et al. Prostaglandin E2 (PGE2) levels as a predictor of type 2 diabetes control in human subjects: A cross-sectional view of initial cohort study data. The FASEB Journal. Meeting Abstracts: Experimental Biology. 2017; 31(Special Issue): 675-76. https://doi.org/10.1096/fasebj.31.1_supplement.675.6. [ Link] [ DOI] 19. Beloqui O, Páramo JA, Orbe J, Benito A, Colina I, Monasterio A, et al. Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors? Eur Heart J. 2005 Jan;26(2):153-58. https://doi.org/10.1093/eurheartj/ehi016. [ DOI] [ PubMed] 20. Khajeniazi S, Marjani A, Shakeri R, Hakimi S. Polymorphism of Secretary PLA2G2A Gene Associated with Its Serum Level in Type2 Diabetes Mellitus Patients in Northern Iran. Endocr Metab Immune Disord Drug Targets. 2019;19(8):1192-97. https://doi.org/10.2174/1871530319666190528111225. [ DOI] [ PubMed] 21. Bosma KJ, Andrei SR, Katz LS, Smith AA, Dunn JC, Ricciardi VF, et al. Pharmacological blockade of the EP3 prostaglandin E2 receptor in the setting of type 2 diabetes enhances β-cell proliferation and identity and relieves oxidative damage. Mol Metab. 2021 Dec;54:101347. https://doi.org/10.1016/j.molmet.2021.101347. [ DOI] [ PubMed] 22. Fenske RJ, Weeks AM, Daniels M, Nall R, Pabich S, Brill AL, et al. Plasma Prostaglandin E2 Metabolite Levels Predict Type 2 Diabetes Status and One-Year Therapeutic Response Independent of Clinical Markers of Inflammation. Metabolites. 2022 Dec;12(12):1234. https://doi.org/10.3390/metabo12121234. [ DOI] [ PubMed] 23. Guan Y, Davis L, Breyer MD, Hao CM. Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor. Prostaglandins Other Lipid Mediat. 2022 Apr;159:106621. https://doi.org/10.1016/j.prostaglandins.2022.106621. [ DOI] [ PubMed] 24. Salah Khalifa A, Elshebiny A, Mohamed Eed E, Elhelbawy MG, Kamal Rizk S. Genetic variations of tumor necrosis factor-α and prostaglandin-endoperoxide synthase 2 genes among Egyptian patients with type 2 diabetes mellitus and diabetic nephropathy. Gene Reports. 2022;29:101678. https://doi.org/10.1016/j.genrep.2022.101678. [ Link] [ DOI] 25. Tan GSQ, Morton JI, Wood S, Trevaskis NL, Magliano DJ, Windsor J, et al. COX2 inhibitor use and type 2 diabetes treatment intensification: A registry-based cohort study. Diabetes Res Clin Pract. 2024 Jan;207:111082. https://doi.org/10.1016/j.diabres.2023.111082. [ DOI] [ PubMed] 26. Suthon S, Tangjittipokin W. Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus. Int J Mol Sci. 2024 Feb;25(4):2039. https://doi.org/10.3390/ijms25042039. [ DOI] [ PubMed] 27. Rafeeinia A, Tabandeh A, Khajeniazi S, Marjani A. Metabolic syndrome in preeclampsia women in gorgan. Open Biochem J. 2014 Dec;8:94-9. https://doi.org/10.2174/1874091x01408010094. [ DOI] [ PubMed] 28. Mourad SA, El Arman MM, Mesbah A, Youssef AR, Gouda T, Nada HS, et al. Cyclooxygenase-2 Gene Variant in Egyptian Patients with Type 2 Diabetes Mellitus with Correlation to Lipid Profile and Markers of Oxidative Stress. Mansoura Medical Journal. 2025;55(1):20-28. https://doi.org/10.58775/2735-3990.1494. [ Link] [ DOI]
|
|
| Send email to the article author |
|
|
|
Hezarjaribi R, Haji Hosseini R, Khajeniazi S. Association between the Cyclooxygenase-2 Gene Polymorphism (-765G>C) and Serum Prostaglandin E2 Levels in Patients with Type 2 Diabetes. J Gorgan Univ Med Sci 2026; 28 (2) :43-51 URL: http://goums.ac.ir/journal/article-1-4640-en.html
|