Volume 11, Issue 4 (11-2025)
Journal of Research in Applied and Basic Medical Sciences 2025, 11(4): 370-376 |
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Putti P, Rohith K, bhaskar Potuganti V, Surya Prabha M L, Aggarwal J, Mohiuddin M, et al . Identification of CTLA-4 +49 A/G (Rs231775) Polymorphism in Diabetic Retinopathy and its Allelic Association with Cardiovascular Disease Risk Factors. Journal of Research in Applied and Basic Medical Sciences 2025; 11 (4) :370-376
URL: http://ijrabms.umsu.ac.ir/article-1-440-en.html
URL: http://ijrabms.umsu.ac.ir/article-1-440-en.html
Praneeth Putti * 
, Karnati Rohith , Vijaya Bhaskar Potuganti , M Lakshmi Surya Prabha , Juhi Aggarwal , Meraj Mohiuddin , Shabana Shireen , Babulal S , Swarna Deepak Kuragayala , Mahaboob Vali Shaik
, Karnati Rohith , Vijaya Bhaskar Potuganti , M Lakshmi Surya Prabha , Juhi Aggarwal , Meraj Mohiuddin , Shabana Shireen , Babulal S , Swarna Deepak Kuragayala , Mahaboob Vali Shaik
Department of Ophthalmology, Mallareddy Institute of Medical Sciences, GHMC Quthbullapur, Jeedimetla, Hyderabad, Telangana, India , praneeth84@gmail.com
Abstract: (73 Views)
Background & Aim: The Study investigates the association between the CTLA-4 +49 A/G (rs231775) polymorphism and cardiovascular disease risk factors in patients with diabetic retinopathy.
Methods & Materials: Fifty cases with diabetic retinopathy were compared to fifty healthy controls. Blood samples were subjected to ARMS-PCR with primers specific to the CTLA-4 +49 A/G (rs231775) gene.
Results: Hypertension was identified as a co-factor for diabetic retinopathy, with an odds ratio of 1.32 (95% CI: 0.45-4.85). Furthermore, the A allele was more frequently observed in patients with a history of myocardial infarction than the G allele, with counts of 25 versus 10 and 11 versus 4 (p = 0.455). The A allele was also more prevalent in the hyperlipidemia group than the G allele, with frequencies of 34 versus 1 and 9 versus 6 (p = 0.255). Hyperlipidemia was recognized as a co-factor for diabetic retinopathy, with an odds ratio of 2.25 (95% CI: 0.42-12.65). The A allele showed an odds ratio of 3.85 (95% CI: 1.95-7.99), indicating an increased risk of developing diabetic retinopathy. The AG genotype was significantly more common in the diabetic retinopathy group compared to the control group (31 versus 11) (p = 0.003), and this genotype was associated with a higher risk for diabetic retinopathy (odds ratio: 12.2, 95% CI: 4.56-41.85). The AA genotype was more frequently observed in the diabetic retinopathy group than the control group (15 versus 22) (p = 0.312) (odds ratio: 3.2, 95% CI: 0.598-7).
Conclusion: The AG genotype and the A allele were more prevalent in patients with diabetic retinopathy, suggesting that they may be risk factors. The AA genotype, the AG genotype, and the G allele exhibited significant associations with diabetic retinopathy.
Methods & Materials: Fifty cases with diabetic retinopathy were compared to fifty healthy controls. Blood samples were subjected to ARMS-PCR with primers specific to the CTLA-4 +49 A/G (rs231775) gene.
Results: Hypertension was identified as a co-factor for diabetic retinopathy, with an odds ratio of 1.32 (95% CI: 0.45-4.85). Furthermore, the A allele was more frequently observed in patients with a history of myocardial infarction than the G allele, with counts of 25 versus 10 and 11 versus 4 (p = 0.455). The A allele was also more prevalent in the hyperlipidemia group than the G allele, with frequencies of 34 versus 1 and 9 versus 6 (p = 0.255). Hyperlipidemia was recognized as a co-factor for diabetic retinopathy, with an odds ratio of 2.25 (95% CI: 0.42-12.65). The A allele showed an odds ratio of 3.85 (95% CI: 1.95-7.99), indicating an increased risk of developing diabetic retinopathy. The AG genotype was significantly more common in the diabetic retinopathy group compared to the control group (31 versus 11) (p = 0.003), and this genotype was associated with a higher risk for diabetic retinopathy (odds ratio: 12.2, 95% CI: 4.56-41.85). The AA genotype was more frequently observed in the diabetic retinopathy group than the control group (15 versus 22) (p = 0.312) (odds ratio: 3.2, 95% CI: 0.598-7).
Conclusion: The AG genotype and the A allele were more prevalent in patients with diabetic retinopathy, suggesting that they may be risk factors. The AA genotype, the AG genotype, and the G allele exhibited significant associations with diabetic retinopathy.
Type of Study: orginal article |
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References
1. Pradeepa R, Mohan V. Epidemiology of type 2 diabetes in India. Indian J Ophthalmol. 2021;69(11):2932-8. doi:10.4103/ijo.IJO_1627_21 [DOI:10.4103/ijo.IJO_1627_21] [PMID] [PMCID]
2. Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes. 2015;6(1):92-108. doi:10.4239/wjd.v6.i1.92 [DOI:10.4239/wjd.v6.i1.92] [PMID] [PMCID]
3. Wang S, Jia Y, Li T, Wang A, Gao L, Yang C, et al. Dry eye disease is more prevalent in children with diabetes than in those without diabetes. Curr Eye Res. 2019;44(12):1299-305. doi: 10.1080/02713683.2019.1641827 [DOI:10.1080/02713683.2019.1641827] [PMID]
4. Lundeen EA, Burke-Conte Z, Rein DB, Wittenborn JS, Saaddine J, Lee AY, et al. Prevalence of diabetic retinopathy in the US in 2021. JAMA Ophthalmol. 2023;141(8):747-54. doi: 10.1001/jamaophthalmol.2023.2289 [DOI:10.1001/jamaophthalmol.2023.2289] [PMID] [PMCID]
5. Wallsh JO, Gallemore RP. Anti-VEGF-resistant retinal diseases: a review of the latest treatment options. Cells. 2021;10(5):1049. doi: 10.3390/cells10051049 [DOI:10.3390/cells10051049] [PMID] [PMCID]
6. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41-7. doi: 10.1038/nature18642 [DOI:10.1038/nature18642] [PMID] [PMCID]
7. Mirsharif ES, Rostamian A, Salehi M, Askari N, Ghazanfari T. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)+ 49A> G (rs231775) gene polymorphism is not associated with COVID-19 severity and mortality in an Iranian population. Heliyon. 2024;10(1). doi: 10.1016/j.heliyon.2023.e23308 [DOI:10.1016/j.heliyon.2023.e23308] [PMID] [PMCID]
8. Lindarto D, Darmadi D. Association Between CTLA4 Level and Obesity, Dyslipidemia, and Type 2 Diabetes Mellitus. Med Arch. 2025;79(2):117. doi: 10.5455/medarh.2025.79.117-121 [DOI:10.5455/medarh.2025.79.117-121] [PMID] [PMCID]
9. Russo G, Manicardi V, Rossi M, Orsi E, Solini A. Sex-and gender-differences in chronic long-term complications of type 1 and type 2 diabetes mellitus in Italy. Nutr Metab and Cardiovasc Dis. 2022;32(10):2297-309. doi:10.1016/j.numecd.2022.08.011 [DOI:10.1016/j.numecd.2022.08.011] [PMID]
10. Zheng W, Chu J, Ren J, Dong J, Bambrick H, Wang N, et al. Age-and gender-specific differences in the seasonal distribution of diabetes mortality in Shandong, China: a spatial analysis. Int J Environ Res Public Health. 2022;19(24):17024. doi: 10.3390/ijerph192417024 [DOI:10.3390/ijerph192417024] [PMID] [PMCID]
11. Alwadeai KS, Alhammad SA. Prevalence of type 2 diabetes mellitus and related factors among the general adult population in Saudi Arabia between 2016-2022: A systematic review and meta-analysis of the cross-sectional studies. Medicine (Baltimore). 2023;102(24):e34021. doi: 10.1097/MD.0000000000034021 [DOI:10.1097/MD.0000000000034021] [PMID] [PMCID]
12. Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, et al. Diabetes in older adults. Diabetes Care. 2012;35(12):2650. doi: 10.2337/dc12-1801 [DOI:10.2337/dc12-1801] [PMID] [PMCID]
13. Berraho M, El Achhab Y, Benslimane A, Rhazi KE, Chikri M, Nejjari C. Hypertension and type 2 diabetes: a cross-sectional study in Morocco (EPIDIAM Study). Pan Afr Med J. 2012;11(1). [Google Scholar]
14. Dong, Y., Zhou, J., Zhu, Y., Luo, L., He, T., Hu, H., ... & Yu, M. (2018). Association between sleep duration and HbA1c level: a systematic review and meta-analysis. Sleep medicine reviews, 48, 66-75.
15. Zhou Z. Jin P, Xiang B, Huang G, The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults. J Endocrinol Invest. 2015;38:149-54. [DOI:10.1007/s40618-014-0162-x] [PMID]
16. Yanagawa T, Taniyama M, Enomoto S, Gomi K, Maruyama H, Ban Y, et al. CTLA4 gene polymorphism confers susceptibility to Graves' disease in Japanese. Thyroid. 1997;7(6):843-6. doi: 10.1089/thy.1997.7.843 [DOI:10.1089/thy.1997.7.843] [PMID]
17. Paterson AM, Lovitch SB, Sage PT, Juneja VR, Lee Y, Trombley JD, et al. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med. 2015;212(10):1603-21. doi: 10.1084/jem.20141030 [DOI:10.1084/jem.20141030] [PMID] [PMCID]
18. Ren D, He L, Pang X. Association of CLTA-4 gene polymorphisms with diabetes mellitus: a study based on the Han population of Northern China. Diabetes Metab Syndr Obes: Targets and Therapy. 2022:2705-12. doi:10.2147/DMSO.S374451 [DOI:10.2147/DMSO.S374451] [PMID] [PMCID]
19. Chang Y-C, Liu P-H, Yu Y-H, Kuo S-S, Chang T-J, Jiang Y-D, et al. Validation of type 2 diabetes risk variants identified by genome-wide association studies in the Han Chinese population: a replication study and meta-analysis. PloS One. 2014;9(4):e95045. doi:10.1371/journal.pone.0095045 [DOI:10.1371/journal.pone.0095045] [PMID] [PMCID]
20. Veitch S, Njock M-S, Chandy M, Siraj MA, Chi L, Mak H, et al. MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes. Cardiovasc Diabetol. 2022;21(1):31. doi: 10.1186/s12933-022-01458-z [DOI:10.1186/s12933-022-01458-z] [PMID] [PMCID]
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