PDF herunterladen
Horm Metab Res 2024; 56(03): 214-222
DOI: 10.1055/a-2223-2790
Original Article: Endocrine Care

Association Between VEGF-460C/T Gene Polymorphism and Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: A Meta-Analysis

Bo Cheng 
1   Department of Ophthalmology, The People’s Hospital of Fenghua, Ningbo, China
,
Aimin Wu
1   Department of Ophthalmology, The People’s Hospital of Fenghua, Ningbo, China
,
Xuewei Zhou
1   Department of Ophthalmology, The People’s Hospital of Fenghua, Ningbo, China
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

Abstract

The aim of the study was to investigate the relationship between VEGF-460C/T polymorphism and susceptibility to diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) by meta-analysis. A comprehensive search was conducted across six databases until September 2023 to identify studies examining the association between VEGF-460C/T polymorphism and susceptibility to DR. Data process was performed by Stata 15.0 software. Eight studies were included, involving 1463 patients with DR. In the overall analysis, the difference was statistically significant only in the homozygous model (CC vs. TT: OR=1.86, p=0.048). A subgroup analysis of 6 papers with genotype frequency satisfying HWE in the control group indicated significant differences among the allele (C vs. T: OR=1.34, p=0.037), recessive (CC vs. CT+TT: OR=1.96, p=0.022) and homozygous (CC vs. TT: OR=2.28, p=0.015) models. However, in the dominant and heterozygous models, the difference was not statistically significant. The sensitivity of the HWE-based subgroup analysis showed that the conclusions in other gene models except the heterozygote model were not robust. This meta-analysis indicated that VEGF-460C/T gene polymorphism is associated with susceptibility to DR in T2DM. Allele C and genotype CC at the VEGF-460C/T locus are associated with an increased risk of DR in T2DM. However, considering that the results are not robust, more trials involving more rigorous design are needed to verify the findings of this review in the future.

Key words

VEGF - type 2 diabetes mellitus - diabetic retinopathy - meta-analysis

Supplementary Material



Publikationsverlauf

Eingereicht: 04. Juli 2023

Angenommen nach Revision: 05. Dezember 2023

Accepted Manuscript online:
05. Dezember 2023

Artikel online veröffentlicht:
25. Januar 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet (London, England) 2010; 376: 124-136
    CrossrefPubMedGoogle Scholar
  • 2 Teo ZL, Tham YC, Yu M. et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 2021; 128: 1580-1591
    CrossrefPubMedGoogle Scholar
  • 3 Hammes H. Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond. Diabetologia 2018; 61: 29-38
    CrossrefPubMedGoogle Scholar
  • 4 Safi SZ, Qvist R, Kumar S. et al. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. Biomed Res Int 2014; 801269
    PubMedGoogle Scholar
  • 5 Zhang J, Zhang J, Zhang C. et al. Diabetic macular edema: current understanding, molecular mechanisms and therapeutic implications. Cells (Basel) 2022; 11: 3362
    PubMedGoogle Scholar
  • 6 Madonna R, Balistreri CR, Geng YJ. et al. Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches. Vasc Pharmacol 2017; 90: 1-7
    CrossrefPubMedGoogle Scholar
  • 7 Leley SP, Ciulla SP, Bhatwadekar AD. Diabetic retinopathy in the aging population: a perspective of pathogenesis and treatment. Clin Interv Aging 2021; 16: 1367-1378
    CrossrefPubMedGoogle Scholar
  • 8 Heng LZ, Comyn O, Peto T. et al. Diabetic retinopathy: pathogenesis, clinical grading, management and future developments. Diabet Med 2013; 30: 640-650
    CrossrefPubMedGoogle Scholar
  • 9 Oshitari T. The pathogenesis and therapeutic approaches of diabetic neuropathy in the retina. Int J Mol Sci 2021; 22: 9050
    CrossrefPubMedGoogle Scholar
  • 10 Maturi RK, Glassman AR, Josic K. et al. Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol W randomized clinical trial. JAMA Ophthalmol 2021; 139: 701-712
    CrossrefPubMedGoogle Scholar
  • 11 Maturi RK, Glassman AR, Josic K. et al. Four-year visual outcomes in the protocol W randomized trial of intravitreous aflibercept for prevention of vision-threatening complications of diabetic retinopathy. JAMA 2023; 329: 376-385
    CrossrefPubMedGoogle Scholar
  • 12 Caldwell RB, Bartoli M, Behzadian MA. et al. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes/Metab Res Rev 2003; 19: 442-455
    CrossrefPubMedGoogle Scholar
  • 13 Radovich M, Hancock BA, Kassem N. et al. Resequencing of the vascular endothelial growth factor promoter reveals haplotype structure and functional diversity. Angiogenesis 2010; 13: 211-218
    CrossrefPubMedGoogle Scholar
  • 14 Xie XJ, Yang YM, Jiang JK. et al. Association between the vascular endothelial growth factor single nucleotide polymorphisms and diabetic retinopathy risk: a meta-analysis. J Diabetes 2017; 9: 738-753
    CrossrefPubMedGoogle Scholar
  • 15 Gong JY, Sun YH. Association of VEGF gene polymorphisms with diabetic retinopathy: a meta-analysis. Plos One 2013; 8: e84069
    CrossrefPubMedGoogle Scholar
  • 16 Han L, Zhang L, Xing W. et al. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies. J Diabetses Res 2014; 805801
    PubMedGoogle Scholar
  • 17 Yang Q, Zhang Y, Zhang X. et al. Association of VEGF gene polymorphisms with susceptibility to diabetic retinopathy: a systematic review and meta-analysis. Horm Metab Res 2020; 52: 264-279
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Hu L, Gong C, Chen X. et al. Associations between vascular endothelial growth factor gene polymorphisms and different types of diabetic retinopathy susceptibility: a systematic review and meta-analysis. J Diabetes Res. 2021 7059139.
    PubMedGoogle Scholar
  • 19 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical research ed.) 2021; 372: n71
    PubMedGoogle Scholar
  • 20 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
    CrossrefPubMedGoogle Scholar
  • 21 Crawford TN, Alfaro DV, Kerrison JB. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev 2009; 5: 8-13
    CrossrefPubMedGoogle Scholar
  • 22 Yang X, Deng Y, Gu H. et al. Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes. Mol Vis 2011; 17: 3088-3096
    PubMedGoogle Scholar
  • 23 Szaflik JP, Wysocki T, Kowalski M. et al. An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy. Graefe's Archiv. Clin Exp Ophthalmol 2008; 246: 39-43
    PubMedGoogle Scholar
  • 24 Paine SK, Basu A, Mondal LK. 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: 2749-2757.
    PubMedGoogle Scholar
  • 25 Yang X, Deng Y, Gu H. et al. Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes. Mol Vis 2014; 20: 200-214
    PubMedGoogle Scholar
  • 26 Yuan Y, Wen Z, Guan Y. et al. The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects. J Diabetes Complicat 2014; 28: 785-791
    CrossrefPubMedGoogle Scholar
  • 27 Khan N, Paterson AD, Roshandel D. et al. Association of IGF1 and VEGFA polymorphisms with diabetic retinopathy in Pakistani population. Acta Diabetol 2020; 57: 237-245
    CrossrefPubMedGoogle Scholar
  • 28 Jehanzeb M, Khan NU, Hussain M. et al. Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa, Pakistan. Mol Biol Rep 2023; 50: 227-234
    CrossrefPubMedGoogle Scholar
  • 29 Wang XM, Jin CJ, Zhang T. et al. The association of gene polymorphism of vascular endothelial growth factor with diabetic retinopathy. Chin J Diabetes 2008; 16: 462-464
    PubMedGoogle Scholar
  • 30 Patel S, Chen H, Tinkham NH. et al. Genetic susceptibility of diabetic retinopathy. Curr Diabetses Rep 2008; 8: 257-262
    CrossrefPubMedGoogle Scholar
  • 31 Koutras A, Kotoula V, Fountzilas G. Prognostic and predictive role of vascular endothelial growth factor polymorphisms in breast cancer. Pharmacogenomics 2015; 16: 79-94
    CrossrefPubMedGoogle Scholar
  • 32 Liu X, Zhou X, Song W. et al. The diagnostic value of circulating VEGF in diabetic retinopathy in Asia: a systematic review and meta-analysis. Ophthal Epidemiol 2023; 30: 230-238
    CrossrefPubMedGoogle Scholar
  • 33 Iglicki M, González DP, Loewenstein A. et al. Next-generation anti-VEGF agents for diabetic macular oedema. Eye (London, England) 2022; 36: 273-277
    CrossrefPubMedGoogle Scholar
  • 34 Ai X, Yu P, Luo L. et al. Berberis dictyophylla F. inhibits angiogenesis and apoptosis of diabetic retinopathy via suppressing HIF-1α/VEGF/DLL-4/Notch-1 pathway. J Ethnopharmacol 2022; 296: 115453
    CrossrefPubMedGoogle Scholar
  • 35 Wang N, Zhang C, Xu Y. et al. Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells. Int J Biol Sci 2021; 17: 4316-4326
    CrossrefPubMedGoogle Scholar