Investigation of the glutathione S-transferase gene M1/T1 and angiotensin converting enzyme gene I/D polymorphism in type 1 diabetic patients and possible association with diabetic microvascular complications

Year 2021, Volume: 7 Issue: 5, 447 - 456, 04.09.2021

Soner Cander , Nizameddin Koca , Pınar Şişman , Özen Öz Gül , Mutlu Karkucak , Adem Deligönül , Canan Ersoy

https://doi.org/10.18621/eurj.827173

Abstract

Objectives: Glutathione S-transferase (GST) polymorphism may play a role in the etiology of type 1 diabetes, as GST is involved to detoxification of reactive oxygen radicals and synthesis of proinflammatory mediators. Genetic polymorphisms in the renin-angiotensin aldosterone system, including angiotensin converting enzyme (ACE) gene insertion-deletion (I/D) polymorphism, can affect the progression of diabetes and diabetic complications. In our study we aimed to investigate the GST and ACE gene I/D polymorphism in type 1 diabetic patients for comparison with population and relationships with diabetic complications.

Methods: A total of 116 type 1 diabetic patients were included to study. ACE polymorphism analyzed in the 71 subjects and GST polymorphism analyzed in the 62 subjects as control groups. Polymorphism of DNA samples was studied by PCR technique. Results compared with control groups and studied according the diabetic complications.

Results: ACE gene DD genotype and D allele ratio in the patient group were significantly higher than control group. GST T1 and GST M1 ratios were similar between patient and control groups. ACE genotype group distributions and GST M1/T1 genotype ratios were not different in terms of obesity, glycemic control, duration of diabetes and hypoglycemia frequency and not changed according to diabetic complications.

Conclusions: DD genotype and D allele ratio in diabetic patient group were found to be significantly higher and so a significant relationship was observed between and ACE I/D gene polymorphism and type 1 diabetes. On the other hand, it was observed that ACE I/D and GST gene polymorphism did not have any significant effect on diabetic microvascular complications.

Keywords

Type 1 Diabetes, ACE gene polymorphism, GST gene polymorphism, Diabetic complications

References

• 1. Tabatabaei-Malazy O, Khodaein M, Bitarafan F, Larijani B, Amoli MM. Polymorphism of antioxidant genes as a target for diabetes management. Int J Mol Cell Med 2017;6:135-47.
• 2. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF diabetes altas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271-81.
• 3. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2016;39(Suppl. 1): S1-119.
• 4. Bekris LM, Shephard C, Peterson M, Hoehna J, Van Yserloo B, Rutledge E, et al. Glutathione-s-transferase M1 and Tı polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity 2005;38:567-75.
• 5. Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005;59:365-73.
• 6. Hayes JD, Flanagan JU, Jowsey IR. Glutatione transferases. Annu Rev Pharmacol Toxicol 2005;45:51-88.
• 7. Seruga M, Makuc J, Zavrsnik M, Cilensek I, Ekart R, Petrovic D. Polymorphism of angiotensin-converting enzyme (rs4340) and diabetic nephropathy in caucasians with type 2 diabetes mellitus. BJMG 2016;19:29-34.
• 8. Rahimi Z, Hasanvand A, Felehgari V. Interaction of MTHFR 1298C with ACE D allele augments the risk of diabetic nephropathy in Western Iran. DNA Cell Biol 2012;31:553-9.
• 9. Movva S, Alluri RV, Komandur S, Vattam K, Eppa K, Mukkavali KK, et al. Relationship of angiotensin-converting enzyme gen plymorphism with nephropathy associated with type 2 diabetes mellitus in Asian Indians. J Diabetes Complications 2007;21:237-41.
• 10. Barseem N, Elsamalehy M. Gene polymorphisms of glutathione-s-transferase T1/M1 in Egyptian children and adolescents with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol 2017;9:138-43.
• 11. Vojkova J, Durdik P, Ciljakova M, Michnova Z, Turcan T, Babusikova E. The association between gene polymorphisms of glutathione-s-transferase T1/M1 and type 1 diabetes in Slovak children and adolescents. Cent Eur J Public Health 2013;21:88-91.
• 12. Hori M, Oniki K, Ueda K, Goto S, Mihara S, Marubayashi T, et al. Combined glutathione-s-transpherase T1 and M1 positive genotype afford protection against type 2 diabetes in Japanese. Pharmacogenomics 2007;8:1307-14.
• 13. Datta SK, Kumar V, Ahmed RS, Tripathi AK, Kalra OP, Banerjee. Effect of GSTM1 and GSTT1 double deletions in the development of oxidative stress in diabetic nephropathy patients. Indian J Biochem Biophys 2010;47: 100-3.
• 14. Lin HJ, Han CY, Bernstein DA, Hsiao W, Lin BK, Hardy S. Ethnic distribution of the glutathione transferase Mu 1-1 (GSTm1) null genotype in 1473 individuals and application to bladder cancer susceptibility. Carcinogenesis 1994;15:1077-81.
• 15. Hibbert ML, Millward BA, Demaine AG. The angiotensin I-converting enzyme (ACE) locus is strongly associated with age and duration of diabetes in patients with type I diabetes. J Diabetes Complications 1997;11: 2-8.
• 16. von Scholten BJ, Theilade S, Lajer M, Rossing P. Urinary alpha and pi glutathione s transferases in adult patients with type 1 diabetes. Nephron Extra 2014;4:127-33.
• 17. Yu ZY, Chen LS, Zhang LC, Zhou TB. Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy. Nephrology (Carlton) 2012;17:480-7.
• 18. Xu HY, Liu MM, Wang X, He XY. Association of angiotensin-converting enzyme insertion/deletion polymorphism with type 1 diabetic nephropathy: a meta-analysis. Ren Fail 2016;38:1320-27.
• 19. Hovnik T, Dolzan V, Bratina NU, Podkrajsek KT, Battelino T. Genetic polymorphisms in genes encoding antioxidant enzymes are associated with diabetic retinopathy in type 1 diabetes. Diabetes Care 2009;32: 2258-62.
• 20. Yang Y, Kao MT, Chang CC, Chung SY, Chen CM, Tsai JJ, et al. Glutathion s-transferase T1 deletion is a risk factor for developing end-stage renal disease in diabetic patients. Int J Med 2004;14: 855-9.
• 21. Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl-Jorgensen K. ISPAD clinical practise consensus guidelines 2006-2007: microvascular and macrovascular complications. Pediatr Diabetes 2007;8:163-70.
• 22. Tarnow L, Cambien F, Rossing P, Nielsen FS, Hansen BV, Lecerf L, et al. Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients. Diabetes 1995;44:489-94.
• 23. Ang L, Jaiswal M, Martin C, Pop-Busui R. Glucose control and diabetic neuropathy. lessons from recent large clinical trials. Curr Diab Rep 2014;14:528.
• 24. Babizhayev MA, Strokov IA, Nosikov VV, Savel’yeva EL, Sitnikov VF, Yegorov YE, et al. The role of oxidative stress in diabetic neuropathy: Generation of free radical species in the glycation reaction and gene polymorphisms encoding antioxidant enzymes to genetic susceptibility to diabetic neuropathy in population of type 1 diabetic patients. Cell Biochem Biophys 2015;71:1425-43.
• 25. Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy. J Res Med Sci 2014;19:1090-8.