COMPREHENSIVE ANALYSIS OF VARIOUS GENES IMPLICATED IN REGULATION OF DIABETIC COMPLICATIONS: A CROSS-SECTIONAL STUDY
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Keywords
Diabetes, Diabetic nephropathy, Gene expression, PCR
Abstract
Objective: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are two of the most devastating microvascular complications caused by hyperglycemia. The current study aims to investigate the co-existence of DN and DR in the polymorphism as well mRNA expression for the following genes: angiotensin converting enzyme (ACE), angiotensinogen (AGT), receptor for advanced glycation end products (RAGE), aldose reductase (ALR2), and vascular endothelial growth factor (VEGF).
Material and Method – This current study included 60 diabetic nephropathy (DN) patients. All participants were divided into two groups: Group 1 (DN+DR) and Group 2 (DN-DR). Polymorphism in all genes was identified by PCR, followed by restriction enzyme. The SPSS version 26.0 software was used to analyse biochemical parameters and the relationship of gene polymorphisms. The Quantitative Reverse Transcriptase PCR (qRT-PCR) amplification method was employed to assess mRNA expression in all genes. The 2DDCt approach was utilized to evaluate the relative expression levels of the ACE, AGT, RAGE, ALR2, and VEGF genes.
Results- The relative mRNA expression of the VEGF gene was found to be significantly higher in the DN+DR group than in the DN-DR group. The association between VEGF gene polymorphism and its relative mRNA expression in the DN+DR group was substantially greater in the ID (p=0.03) and DD (p=0.01) genotypes than in the DN-DR group.
Conclusion- The association of VEGF gene polymorphism and its relative mRNA expression levels with the prevalence of diabetic retinopathy was significant. It suggests that the VEGF gene has a unique function in DR patients with DN.
References
2. Misra A, Gopalan H, Jayawardena R, Hills AP, et al. Diabetes in developing countries. Journal of diabetes. 2019;11(7):522-39.
3. Ojo O. An overview of diabetes and its complications. Diabetes Research Open Journal. 2016;2(2): e4-6.
4. Kare P, Aggrawal N, Varshney P, Ghosh R, et al. Screening of Type 2 Diabetes Mellitus Patients for Micro-albuminuria and Its Relationship with Diabetic Retinopathy. International Journal of Biochemistry Research & Review. 2016;14(4):1-9.
5. Rani PK, Raman R, Gupta A, Pal SS, et al. Albuminuria and diabetic retinopathy in type 2 diabetes mellitus sankara nethralaya diabetic retinopathy epidemiology and molecular genetic study (SN-DREAMS, report 12). Diabetology & metabolic syndrome. 2011;3(1):1-8.
6. Konoshita T, Wakahara S, Mizuno S, Motomura M, et al. Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy. Diabetes Care. 2006;29(4):848-52.
7. Bortoloso E, Del Prete D, Dalla Vestra M, Gambaro G, et al. Quantitave and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes. European Journal of Endocrinology. 2004;150(6):799-807.
8. Paul M, Wagner J, Dzau VJ. Gene expression of the renin-angiotensin system in human tissues. Quantitative analysis by the polymerase chain reaction. The Journal of clinical investigation. 1993;91(5):2058-64.
9. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. New England Journal of Medicine. 1988;318(20):1315-21.
10. Ruderman NB, Williamson JR, Brownlee M. Glucose and diabetic vascular disease 1. The FASEB journal. 1992;6(11):2905-14.
11. Kyselova Z, Stefek M, Bauer V. Pharmacological prevention of diabetic cataract. Journal of Diabetes and its Complications. 2004;18(2):129-40.
12. Larkins RG, Dunlop ME. The link between hyperglycaemia and diabetic nephropathy. Diabetologia. 1992;35:499-504.
13. Caldwell RB, Bartoli M, Behzadian MA, El‐Remessy AE, et al. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes/metabolism research and reviews. 2003;19(6):442-55.
14. American Diabetes Association. 1. Promoting health and reducing disparities in populations. Diabetes Care. 2017;40(Supplement_1):S6-10.
15. Rossing K, Christensen PK, Hovind P, Tarnow L, et al. Progression of nephropathy in type 2 diabetic patients. Kidney international. 2004 ;66(4):1596-605.
16. Gheith O, Farouk N, Nampoory N, Halim MA, et al. Diabetic kidney disease: worldwide difference of prevalence and risk factors. Journal of nephropharmacology. 2016;5(1):49.
17. Alemu Mersha G, Alimaw YA, Woredekal AT. Prevalence of diabetic retinopathy among diabetic patients in Northwest Ethiopia—A cross sectional hospital-based study. Plos one. 2022 ;17(1): e0262664.
18. Cahn A, Cernea S, Raz I. The SONAR study—is there a future for endothelin receptor antagonists in diabetic kidney disease? Annals of Translational Medicine. 2019;7(Suppl 8).
19. Zhang Y, Li W, Zhou Y. Identification of hub genes in diabetic kidney disease via multiple-microarray analysis. Annals of Translational Medicine. 2020 ;8(16).
20. Brenner BM, Cooper ME, De Zeeuw D, Keane WF, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. New England journal of medicine. 2001 ;345(12):861-9.
21. Van Leiden HA, Dekker JM, Moll AC, Nijpels G, et al. Blood pressure, lipids, and obesity are associated with retinopathy: the hoorn study. Diabetes care. 2002;25(8):1320-5.
22. Wan H, Wang Y, Xiang Q, Fang S, et al. Associations between abdominal obesity indices and diabetic complications: Chinese visceral adiposity index and neck circumference. Cardiovascular Diabetology. 2020; 19:1-2.
23. Rajalakshmi R, Rani CS, Venkatesan U, Unnikrishnan R, et al. Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population. BMJ open diabetes research & care. 2020;8(1).
24. Kaewput W, Thongprayoon C, Rangsin R, Ruangkanchanasetr P, et al. Associations of renal function with diabetic retinopathy and visual impairment in type 2 diabetes: A multicenter nationwide cross-sectional study. World journal of nephrology. 2019 ;8(2):33.
25. Sacks FM, Hermans MP, Fioretto P, Valensi P, et al. Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case–control study in 13 countries. Circulation. 2014;129(9):999-1008.
26. Sasso FC, Pafundi PC, Gelso A, Bono V, et al. High HDL cholesterol: A risk factor for diabetic retinopathy? Findings from NO BLIND study. Diabetes research and clinical practice. 2019; 150:236-44.
27. Khan SZ, Ajmal N, Shaikh R. Diabetic retinopathy and vascular endothelial growth factor gene insertion/deletion polymorphism. Canadian Journal of Diabetes. 2020;44(3):287-91.
28. Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, Jozwiak L. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrology dialysis transplantation. 2007;22(3):827-32.
29. Miura J, Uchigata Y, Yokoyama H, Omori Y, et al. Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. Diabetes research and clinical practice. 1999;45(1):41-9.
30. Cha DR, Kang YS, Han SY, Jee YH, et al. Vascular endothelial growth factor is increased during early stage of diabetic nephropathy in type II diabetic rats. Journal of Endocrinology. 2004;183(1):183-94.
31. Pe’er J, Folberg R, Itin A, Gnessin H, et al. Vascular endothelial growth factor upregulation in human central retinal vein occlusion. Ophthalmology. 1998 ;105(3):412-6.
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Parul Gupta
Department of Endocrinology1, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, 110095, Delhi, India.
Sri Venkata Madhu
Director Professor Department of Endocrinology, UCMS and GTB hospital Dilshad Garden, New Delhi- 110095, India, ORCHID ID- 0000-0003-0018-5984 Mob-91-9871891018
Parvesh Bubber
Biochemistry Discipline, School of Sciences 2, Indira Gandhi National Open University, Maidan Garhi,110068, New Delhi, India.
Neerja Aggarwal
Department of Radiology, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, 110095, Delhi, India