The Relationship Between AKR1B1 rs759853 (C-106T) Polymorphism and the Diabetic Retinopathy Severity in Turkish Type 2 Diabetes Mellitus Patients

An Erratum to this article was published on May 15, 2023. https://dergipark.org.tr/tr/pub/medr/article/1409630

Abstract

Aim: Diabetes mellitus (DM) is an important health problem with an increasing incidence worldwide and causes many complications. Diabetic retinopathy (DR) is one of the most serious complications of DM. Polymorphisms of the AKR1B1 gene, which encodes an aldose reductase enzyme, have been associated with development of DM and DR in some studies. The current study aims to investigate the relationship of AKR1B1 rs759853 polymorphism with type 2 DM (T2DM), DR and DR severity in the Turkish population.
Materials and Methods: A total of 437 individuals, including 141 T2DM patients without DR, 125 T2DM patients with DR, and 171 healthy controls, were included in the study. Genotyping was performed using PCR-RFLP method.
Results: An association between T allele / TT genotype and increased risk of proliferative diabetic retinopathy (PDR) was detected. In the logistic regression analysis in which other risk factors were included, rs759853 polymorphism and diabetes duration were found to be associated with the PDR development. There was no significant relationship between the AKR1B1 rs759853 variation and the development of T2DM and DR.
Conclusion: Obtained data showed that AKR1B1 rs759853 polymorphism is not associated with the development of T2DM and DR in the Turkish patients, but TT genotype and diabetes duration are independent risk factors for the development of PDR.

Keywords

• Type 2 diabetes mellitus
• diabetic retinopathy
• AKR1B1
• aldose reductase
• rs759853
• polymorphism

Kaynakça

1. 1. IDF DIABETES ATLAS Ninth edition 2019 https://www.diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf access date 20.10.2022
2. 2. Fan WY, Gu H, Yang XF, et al. Association of candidate gene polymorphisms with diabetic retinopathy in Chinese patients with type 2 diabetes. Int J Ophthalmol. 2020;13:301.
3. 3. Ghamdi AH Al. Clinical Predictors of Diabetic Retinopathy Progression; A Systematic Review. Curr Diabetes Rev. 2019;16:242–7.
4. 4. TURKDİAB. TÜRKDİAB Diyabet tanı ve tedavi rehberi 2019 https://www.turkdiab.org/admin/PICS/files/Diyabet_Tani_ve_Tedavi_Rehberi_2019.pdf access time 20.10.2022
5. 5. Lin KY, Hsih WH, Lin YB, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig. 2021;12:1322.
6. 6. Cao M, Tian Z, Zhang L, et al. Genetic association of AKR1B1 gene polymorphism rs759853 with diabetic retinopathy risk: A meta-analysis. Gene. 2018;676:73–8.
7. 7. Dieter C, Lemos NE, de Faria Corrêa NR, et al. The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population. Arch Endocrinol Metab. 2022;66:12–8.
8. 8. Balestri F, Moschini R, Mura U, et al. In Search of Differential Inhibitors of Aldose Reductase. Biomolecules. 2022;12:485.

9. 9. Donaghue KC, Margan SH, Chan AKF, et al. The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents. Diabet Med. 2005;22:1315–20.
10. 10. Watarai A, Nakashima E, Hamada Y, et al. Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients. Diabet Med. 2006;23:894–9.
11. 11. Mrozikiewicz-Rakowska B, Lukawska M, Nehring P, et al. Genetic predictors associated with diabetic retinopathy in patients with diabetic foot. Polish Arch Intern Med. 2018;128:926–33.
12. 12. Kaur N, Vanita V. Association of aldose reductase gene (AKR1B1) polymorphism with diabetic retinopathy. Diabetes Res Clin Pract. 2016;121:41–8.
13. 13. Richeti F, Noronha RM, Waetge RTL, et al. Evaluation of AC(n) and C(-106)T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy. Mol Vis. 2007;13:740.
14. 14. Abu-Hassan D, Al-Bdour M, Saleh I, et al. The relationship between aldose reductase gene C106T polymorphism and the severity of retinopathy in Type 2 diabetic patients: A case–control study. J Res Med Sci. 2021;26:2.
15. 15. Katakami N, Kaneto H, Takahara M, et al. Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2011;92: e57-60.
16. 16. Olmos P, Bastías MJ, Vollrath V, et al. C(-106)T polymorphism of the aldose reductase gene and the progression rate of diabetic retinopathy. Diabetes Res Clin Pract. 2006;74:175–82. 17. Petrovič MG, Peterlin B, Hawlina M, Petrovič D. Aldose reductase (AC)n gene polymorphism and susceptibility to diabetic retinopathy in Type 2 diabetes in Caucasians. J Diabetes Complications. 2005;19:70–3.
17. 18. Li W, Chen S, Mei Z, et al. Polymorphisms in Sorbitol-Aldose Reductase (Polyol) Pathway Genes and Their Influence on Risk of Diabetic Retinopathy Among Han Chinese. Med Sci Monit. 2019;25:7073.
18. 19. Dos Santos KG, Canani LH, Gross JL, et al. The -106CC genotype of the aldose reductase gene is associated with an increased risk of proliferative diabetic retinopathy in Caucasian-Brazilians with type 2 diabetes. Mol Genet Metab. 2006;88:280–4.
19. 20. Abu-Hassan D, Al-Bdour M, Saleh I, et al. The relationship between aldose reductase gene C106T polymorphism and the severity of retinopathy in Type 2 diabetic patients: A case-control study. J Res Med Sci. 2021;26:2.
20. 21. Shawki HA, Abo-hashem EM, Youssef MM, et al. PPAR2, aldose reductase, and TCF7L2 gene polymorphisms: relation to diabetes mellitus. J Diabetes Metab Disord. 2022;21:241–50.
21. 22. Sivenius K, Pihlajamäki J, Partanen J, et al. Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 Diabetes. Diabetes Care. 2004;27:2021–6.
22. 23. Deng Y, Yang XF, Gu H, et al. Association of C(-106)T polymorphism in aldose reductase gene with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Chinese Med Sci J. 2014;29:1–6.
23. 24. Santos KG, Tschiedel B, Schneider J, et al. Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: Relationship with polymorphisms in the aldose reductase, the plasminogen activator inhibitor-1 and the methylenetetrahydrofolate reductase genes. Diabetes Res Clin Pract. 2003;61:133–6.
24. 25. Zhou M, Zhang P, Xu X, Sun X. The Relationship Between Aldose Reductase C106T Polymorphism and Diabetic Retinopathy: An Updated Meta-Analysis. Invest Ophthalmol Vis Sci. 2015;56:2279–89.
25. 26. Lin S, Peng Y, Cao M, et al. Association between Aldose Reductase Gene C(-106)T Polymorphism and Diabetic Retinopathy: A Systematic Review and Meta-Analysis. Ophthalmic Res. 2020;63:224–33.
26. 27. Fu ZJ, Li SY, Kociok N, et al. Aldose reductase deficiency reduced vascular changes in neonatal mouse retina in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2012;53:5698–712.
27. 28. Yang B, Millward A, Demaine A. Functional differences between the susceptibility Z−2/C−106 and protective Z+2/T−106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications. Biochim Biophys Acta - Mol Basis Dis. 2003;1639:1–7.