Relationship of rs1800470 polymorphism of TGFB1 gene with diabetic retinopathy in type 2 diabetes

Authors

  • A. S. Hudz Danylo Halytsky Lviv National Medical University https://orcid.org/0009-0009-0146-6367
  • V. O. Sergiienko Danylo Halytsky Lviv National Medical University
  • I. V. Kudryl Danylo Halytsky Lviv National Medical University
  • S. Yu. Mogilevskyy Shupyk National Healthcare University of Ukraine
  • A. O. Gulida Shupyk National Healthcare University of Ukraine
  • S. V. Ziablitsev Bohomolets National Medical University

DOI:

https://doi.org/10.31288/oftalmolzh2025238

Keywords:

T2DM, diabetic retinopathy, rs1800470, TGFB1, central retinal thickness, central retinal volume, retina

Abstract

Purpose: To investigate the relationship between rs1800470 polymorphism of TGFB1 gene and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM).
Material and Methods: Totally, 102 type 2 diabetes (T2DM) patients with DR were examined and divided into groups based on the stage of DR: group 1 (non-proliferative DR (NPDR), 35 patients), group 2 (pre-proliferative DR (PPDR), 34 patients), and group 3 (proliferative DR (PDR), 33 patients). The control group was composed of 61 individuals. Patients underwent a routine eye examination. rs1800470 (Т869С; L10P) genotypes were determined by real time polymerase chain reaction (PCR) using Gene Amp® 7500 PCR System (Applied Biosystems, Foster City, CA) and TaqMan Mutation Detection Assays (Life Technologies, Carlsbad, CA).
Results: The ancestral GG genotype tended to be less frequent, whereas the minor AA genotype (and, correspondingly, the minor A allele) tended to be more frequent in patients with DR compared with controls. The minor AA genotype and, consequently, the minor A allele were more frequent in patients with a more severe DR, but the difference was not significant (р > 0.05). We found an association of rs1800470 genotype with the phenotype of DR: BCVA was lower (р = 0.016) and CRT and CRV were larger (р < 0.001 for both comparisons) in carriers of the minor AA genotype of rs1800470 compared to carriers of the ancestral GG genotype. After stratification of patients by the stage of DR, the greatest distinction in parameters among carriers of different genotypes was seen in PDR: in carriers of the AA genotype, CRT and CRV were 2.5 times and 1.4 times, respectively, larger, than in carriers of the GG genotype (p < 0.001).
Conclusion: rs1800470 polymorphism of TGFB1 gene affected the course of DR, which was more pronounced in PDR.

Author Biographies

A. S. Hudz , Danylo Halytsky Lviv National Medical University

S. Hudz, Dr Sc (Med), Prof., Danylo Halytsky Lviv National Medical University, Lviv (Ukraine)

V. O. Sergiienko , Danylo Halytsky Lviv National Medical University

O. Serhiyenko, Dr Sc (Med), Prof., Danylo Halytsky Lviv National Medical University, Lviv (Ukraine)

I. V. Kudryl, Danylo Halytsky Lviv National Medical University

V. Kudryl, Dr Sc (Med), Assistant, Danylo Halytsky Lviv National Medical University, Lviv (Ukraine)

S. Yu. Mogilevskyy, Shupyk National Healthcare University of Ukraine

Yu. Mogilevskyy, Dr Sc (Med), Prof., Shupyk National Healthcare University of Ukraine, Kyiv (Ukraine)

A. O. Gulida, Shupyk National Healthcare University of Ukraine

O. Gulida, Cand Sc (Med), Assistant, Shupyk National University of Health Care of Ukraine, Kyiv (Ukraine)

S. V. Ziablitsev, Bohomolets National Medical University

V. Ziablitsev, MD, Full Professor Bohomolets National Medical University, Kyiv (Ukraine)

References

American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(1):17-38. https://doi.org/10.2337/dc22-S002

Gregg EW, Buckley J, Ali MK, Davies J, Flood D, Mehta R et al. Global Health and Population Project on Access to Care for Cardiometabolic Diseases. Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact. Lancet. 2023;401(10384):1302-1312. https://doi.org/10.1016/S0140-6736(23)00001-6

Bonora E, Trombetta M, Dauriz M. Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9. BMJ Open Diabetes Res Care 2020;8:e001549. https://doi.org/10.1136/bmjdrc-2020-001549

Hachana S, Larrivée B. TGF-β superfamily signaling in the eye: implications for ocular pathologies. Cells. 2022;11(15):2336. https://doi.org/10.3390/cells11152336

Liu H, Chen YG. The interplay between TGF-β signaling and cell metabolism. Front Cell Dev Biol. 2022;10:846723. https://doi.org/10.3389/fcell.2022.846723

Mesquida M, Drawnel F, Fauser S. The role of inflammation in diabetic eye disease. Semin Immunopathol. 2019;41(4):427-45. https://doi.org/10.1007/s00281-019-00750-7

Mason RH, Minaker SA, Luna GL, Bapat P, Farahvash A, GargA et al. Changes in aqueous and vitreous inflammatory cytokine levels in nonproliferative diabetic retinopathy: a systematic review and meta-analysis. Can J Ophthalmol. 2024:4182(24):173. https://doi.org/10.1016/j.jcjo.2024.05.031

Saucedo L, Pfister IB, Zandi S, Gerhardt C, Garweg JG. Ocular TGF-β, matrix metalloproteinases, and TIMP-1 increase with the development and progression of diabetic retinopathy in type 2 diabetes mellitus. Mediators Inflamm. 2021;2021:9811361. https://doi.org/10.1155/2021/9811361

Zhou D, Mou X, Liu K, Liu W, Xu Y, Zhou D. Association Between Transforming Growth Factor-β1 T869C Gene Polymorphism and Diabetic Nephropathy: A Meta-Analysis in the Chinese Population. Clin Lab. 2019 Jul 1;65(7). https://doi.org/10.7754/Clin.Lab.2019.181238

Rodrigues KF, Pietrani NT, Sandrim VC, Vieira CM, Fernandes AP, Bosco AA et al. Association of a Large Panel of Cytokine Gene Polymorphisms with Complications and Comorbidities in Type 2 Diabetes Patients. J Diabetes Res. 2015;2015:605965. https://doi.org/10.1155/2015/605965

Paine SK, Basu A, Mondal LK, Sen A, Choudhuri S, Chowdhury IH, et al. Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes. Mol Vis. 2012;18:2749-57.

Liu L, Jiao J, Wang Y, Wu J, Huang D, Teng W, Chen L. TGF-beta1 gene polymorphism in association with diabetic retinopathy susceptibility: a systematic review and meta-analysis. PLoS One. 2014 Apr 7;9(4):e94160. https://doi.org/10.1371/journal.pone.0094160

e!Ensemble. Human (GRCh38.p14). Variant rs1800470. Ensembl release 113 - October 2024 © EMBL-EBI. Hinxton, Cambridge, United Kingdom [cited 2025 March 06]. Available from: http://www.ensembl.org/Homo_sapiens/Variation/Explore?db=core;r=19:41352516-41353516;v=rs1800470;vdb=variation;vf=1024617525.

Costa AR, Dieter C, Canani LH, Assmann TS, Crispim D. The rs1800469 T/T and rs1800470 C/C genotypes of the TGFB1 gene confer protection against diabetic retinopathy in a Southern Brazilian population. Genet Mol Biol. 2023;46(3):e20220247. https://doi.org/10.1590/1678-4685-gmb-2022-0247

Beránek M, Kanková K, Benes P, Izakovicová-Hollá L, Znojil V, Hájek D, et al. Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF-beta1) is a newly identified risk factor for proliferative diabetic retinopathy. Am J Med Genet. 2002;109(4):278-83. https://doi.org/10.1002/ajmg.10372

Wong TY, Poon P, Chow KM, Szeto CC, Cheung MK, Li PK. Association of transforming growth factor-beta (TGF-beta) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese. Kidney Int. 2003 May;63(5):1831-5. https://doi.org/10.1046/j.1523-1755.2003.00919.x

Buraczynska M, Baranowicz-Gaszczyk I, Borowicz E, Ksiazek A. TGF-beta1 and TSC-22 gene polymorphisms and susceptibility to microvascular complications in type 2 diabetes. Nephron Physiol. 2007;106(4):p69-75. https://doi.org/10.1159/000104874

Mihoubi E, Amroun H, Bouldjennet F, Azzouz M, Touil-Boukoffa C, Raache R, et al. Polymorphismes 869C> T et 915 G>C du TGF-β1 dans la rétinopathie du diabète de type 1 chez la population algérienne [The 869C>T And 915G>C Polymorphisms of TGF-β1 and Type 1 Diabetic Retinopathy in the Algerian Population]. J FrOphtalmol. 2022 Oct;45(8):908-914. French. https://doi.org/10.1016/j.jfo.2022.02.024

Published

2025-04-30

How to Cite

1.
Hudz AS, Sergiienko VO, Kudryl IV, Mogilevskyy SY, Gulida AO, Ziablitsev SV. Relationship of rs1800470 polymorphism of TGFB1 gene with diabetic retinopathy in type 2 diabetes. J.ophthalmol. (Ukraine) [Internet]. 2025 Apr. 30 [cited 2025 May 7];(2):3-8. Available from: https://ua.ozhurnal.com/index.php/files/article/view/251

Issue

Section

Clinical Ophthalmology