Startseite Association of angiotensin converting enzyme gene insertion/deletion polymorphism with diabetic retinopathy in middle-aged Indians with type 2 diabetes mellitus
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with diabetic retinopathy in middle-aged Indians with type 2 diabetes mellitus

  • Pramita Dutta , Sambuddha Ghosh ORCID logo EMAIL logo , Anindya Dasgupta ORCID logo und Swati Majumder
Veröffentlicht/Copyright: 30. Juli 2024
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Objectives

There are conflicting reports regarding the association of angiotensin 1 converting enzyme (ACE) gene polymorphism with diabetic retinopathy (DR). We compared ACE gene insertion/deletion (I/D) polymorphism between patients with and without DR in a middle-aged Indian population. The secondary outcome measure was the comparison of ACE gene I/D polymorphism in different grades of DR severity.

Methods

Institutional cross-sectional case-control study with middle-aged (45–64 years) type 2 diabetes patients from Eastern India with DR (DR group) and without DR (NODR group). Polymerase chain reaction (PCR) was used to determine the ACE gene I/D polymorphism through primers flanking the polymorphic region of 287 bp Alu repeat sequence in intron 16.

Results

Genotyping for the ACE gene I/D polymorphisms were done for 107 patients in each group. The presence of DR had no significant association with the prevalence of ACE I/D genotype compared to those without DR either in the recessive model (p=0.588) or in the dominant model (p=0.891). The allele contrast was also similar between DR and NODR (p=0.837) groups. The severity of retinopathy was associated with the ACE I/D genotype in the recessive model (p=0.043) but not in the dominant model (p=0.136). However, the severity of retinopathy was associated with allele contrast (p=0.016).

Conclusions

The ACE gene polymorphism was not associated with diabetic retinopathy in middle-aged Indian patients with type 2 diabetes in our study. However, the severity of DR was associated with the ACE gene polymorphism in these patients.


Corresponding author: Sambuddha Ghosh, Professor, Department of Ophthalmology, Calcutta National Medical College, Kolkata, 700014, India, E-mail:
Work done at: Department of Ophthalmology and Department of Biochemistry, Calcutta National Medical College, Kolkata, India.
  1. Research ethics: Prior permission for the study was obtained from the ethics committee of our institute (EC registration number (CDSCO)-ECR/771/Inst/Wb/2015) and the study was conducted in accordance with the declaration of Helsinki (as revised in 2013).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Pramita Dutta, Swati Majumder, Anindya Dasgupta. The first draft of the manuscript was written by Sambuddha Ghosh and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

  4. Competing interests: None.

  5. Research funding: None declared.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Yau, JW, Rogers, SL, Kawasaki, R, Lamoureux, EL, Kowalski, JW, Bek, T, et al.. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012;35:556–64. https://doi.org/10.2337/dc11-1909.Suche in Google Scholar PubMed PubMed Central

2. Lin, KY, Hsih, WH, Lin, YB, Wen, CY, Chang, TJ. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig 2021;12:1322–5. https://doi.org/10.1111/jdi.13480.Suche in Google Scholar PubMed PubMed Central

3. Migdalis, IN, Iliopoulou, VI, Kalogeropoulou, KO, Koutoulidis, KO, Samartzis, MI. Elevated serum levels of angiotensin-converting enzyme in patients with diabetic retinopathy. South Med J 1990;83:425–7. https://doi.org/10.1097/00007611-199004000-00016.Suche in Google Scholar

4. Chaturvedi, N. Modulation of the renin-angiotensin system and retinopathy. Heart 2001;84:i29–31. https://doi.org/10.1136/heart.84.suppl_1.i29. discussion i50.Suche in Google Scholar PubMed PubMed Central

5. Wilkinson-Berka, JL, Agrotis, A, Deliyanti, D. The retinal renin-angiotensin system: roles of angiotensin II and aldosterone. Peptides 2012;36:142–50. https://doi.org/10.1016/j.peptides.2012.04.008.Suche in Google Scholar PubMed

6. Fletcher, EL, Phipps, JA, Ward, MM, Vessey, KA, Wilkinson-Berka, JL. The renin-angiotensin system in retinal health and disease: its influence on neurons, glia and the vasculature. Prog Retin Eye Res 2010;29:284–311. https://doi.org/10.1016/j.preteyeres.2010.03.003.Suche in Google Scholar PubMed

7. Ohno, T, Kawazu, S, Tomono, S. Association analyses of the polymorphisms of angiotensin-converting enzyme and angiotensinogen genes with diabetic nephropathy in Japanese non-insulin-dependent diabetics. Metabolism 1996;45:218–22. https://doi.org/10.1016/s0026-0495(96)90057-8.Suche in Google Scholar PubMed

8. Huang, K, Liang, Y, Wang, K, Ma, Y, Wu, J, Luo, H, et al.. Elevated ACE levels indicate diabetic nephropathy progression or companied retina impaired. Front Clin Diabetes Healthc 2022;3:831128. https://doi.org/10.3389/fcdhc.2022.831128.Suche in Google Scholar PubMed PubMed Central

9. Abhary, S, Hewitt, AW, Burdon, KP, Craig, JE. A systematic meta-analysis of genetic association studies for diabetic retinopathy. Diabetes 2009;58:2137–47. https://doi.org/10.2337/db09-0059.Suche in Google Scholar PubMed PubMed Central

10. McKenzie, CA, Julier, C, Forrester, T, McFarlane-Anderson, N, Keavney, B, Lathrop, GM, et al.. Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: evidence for two quantitative-trait loci. Am J Hum Genet 1995;57:1426–35. Erratum in: Am J Hum Genet 1996;58(3):648.Suche in Google Scholar

11. Rigat, B, Hubert, C, Alhenc-Gelas, F, Cambien, F, Corvol, P, Soubrier, F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–6. https://doi.org/10.1172/jci114844.Suche in Google Scholar

12. Nikzamir, A, Rashidi, A, Esteghamati, A, Nakhjavani, M, Golmohammadi, T, Khalilzadeh, O. The relationship between ACE gene insertion/deletion polymorphism and diabetic retinopathy in Iranian patients with type 2 diabetes. Ophthalmic Genet 2010;31:108–13. https://doi.org/10.3109/13816810.2010.482554.Suche in Google Scholar PubMed

13. Danser, AJ, Schalekamp, MA, Bax, WA, van den Brink, AM, Saxena, PR, Riegger, GA, et al.. Angiotensin-converting enzyme in the human heart: effect of the deletion/insertion polymorphism. Circulation 1995;92:1387–8. https://doi.org/10.1161/01.cir.92.6.1387.Suche in Google Scholar PubMed

14. Ergen, AH, Hatemi, H, Agachan, B, Camlica, H, Isbir, T. Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Exp Mol Med 2004;36:345–50. https://doi.org/10.1038/emm.2004.45.Suche in Google Scholar PubMed

15. Yang, M, Chang-chun, Q, Qun, X, Hong-ding, X. Association of angiotensin converting enzyme gene I/D polymorphism with type 2 diabetes mellitus. Biomed Environ Sci 2006;19:323–7.Suche in Google Scholar

16. Zhou, D, Ruiter, R, Zhang, J, Zhou, M, Liu, H, Liu, W, et al.. Angiotensin-converting enzyme I/D polymorphism is not associated with type 2 diabetes in a Chinese population. J Renin Angiotensin Aldosterone Syst 2012;13:372–8. https://doi.org/10.1177/1470320311435535.Suche in Google Scholar PubMed

17. Chmaisse, HN, Jammal, M, Fakhoury, H, Fakhoury, R. Study on the association between angiotensin-I converting enzyme I/D dimorphism and type-2 diabetes mellitus. Saudi J Kidney Dis Transpl 2009;20:1038–46.Suche in Google Scholar

18. Globocnik-Petrovic, M, Hawlina, M, Peterlin, B, Petrovic, D. Insertion/deletion plasminogen activator inhibitor 1 and insertion/deletion angiotensin-converting enzyme gene polymorphisms in diabetic retinopathy in type 2 diabetes. Ophthalmologica 2003;217:219–24. https://doi.org/10.1159/000068975.Suche in Google Scholar PubMed

19. Walid, AD, Al-Bdour, MD, El-Khateeb, M. Lack of relationship between Alu repetitive elements in angiotensin converting enzyme and the severity of diabetic retinopathy. J Med Biochem 2021;40:302–9. https://doi.org/10.5937/jomb0-27885.Suche in Google Scholar PubMed PubMed Central

20. Zhou, JB, Yang, JK. Angiotensin-converting enzyme gene polymorphism is associated with proliferative diabetic retinopathy: a meta-analysis. Acta Diabetol 2010;47:187–93. https://doi.org/10.1007/s00592-009-0160-1.Suche in Google Scholar PubMed

21. 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.Suche in Google Scholar

22. Cheema, BS, Kohli, HS, Sharma, R, Shah, VN, Bhansali, A, Khullar, M. Angiotensin-converting enzyme gene variants interact with the renin-angiotensin system pathway to confer risk and protection against type 2 diabetic retinopathy. J Diabetes Investig 2013;4:103–4. https://doi.org/10.1111/jdi.12028.Suche in Google Scholar PubMed PubMed Central

23. Saleem, S, Azam, A, Maqsood, SI, Muslim, I, Bashir, S, Fazal, N, et al.. Role of ACE and PAI-1 polymorphisms in the development and progression of diabetic retinopathy. PLoS One 2015;10:e0144557. https://doi.org/10.1371/journal.pone.0144557.Suche in Google Scholar PubMed PubMed Central

24. Lu, Y, Ge, Y, Hu, Q, Shi, Y, Xue, C, Shi, Y, et al.. Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population. J Renin Angiotensin Aldosterone Syst 2012;13:289–95. https://doi.org/10.1177/1470320311432187.Suche in Google Scholar PubMed

25. Wild, S, Roglic, G, Green, A, Sicree, R, King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–53. https://doi.org/10.2337/diacare.27.10.2569-a.Suche in Google Scholar

26. Raman, R, Rani, PK, Rachepalle, SR, Gnanamoorthy, P, Uthra, S, Kumaramanickavel, G, et al.. Prevalence of diabetic retinopathy in India: Sankara Nethralaya diabetic retinopathy epidemiology and molecular genetics study report 2. Ophthalmology 2009;116:311–8. https://doi.org/10.1016/j.ophtha.2008.09.010.Suche in Google Scholar PubMed

27. American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes. Diabetes Care 2020;43:S14. https://doi.org/10.2337/dc20-s002.Suche in Google Scholar

28. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 1991;98:786–806.10.1016/S0161-6420(13)38012-9Suche in Google Scholar

29. Luo, S, Shi, C, Wang, F, Wu, Z. Association between the angiotensin-converting enzyme (ACE) genetic polymorphism and diabetic retinopathy – a meta-analysis comprising 10,168 subjects. Int J Environ Res Public Health 2016;13:1142. https://doi.org/10.3390/ijerph13111142.Suche in Google Scholar PubMed PubMed Central

30. Khan, SU, Qayyum, A, Hussain, SS. Prognostic significance of ACE and PAI-1 genes polymorphisms with diabetic retinopathy and diabetic non-retinopathy in type 2 diabetes. Acta Med Int 2015;2:43–50. https://doi.org/10.5530/ami.2015.3.0.Suche in Google Scholar

31. Zhou, MS, Schulman, IH, Raij, L. Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension. Am J Physiol Heart Circ Physiol 2009;296:H833–9. https://doi.org/10.1152/ajpheart.01096.2008.Suche in Google Scholar PubMed

32. Hsueh, WA, Wyne, K. Renin-angiotensin-aldosterone system in diabetes and hypertension. J Clin Hypertens 2011;13:224–37. https://doi.org/10.1111/j.1751-7176.2011.00449.x.Suche in Google Scholar PubMed PubMed Central

Received: 2023-11-30
Accepted: 2024-07-08
Published Online: 2024-07-30

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 30.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hmbci-2023-0081/pdf?lang=de
Button zum nach oben scrollen