Horm Metab Res
DOI: 10.1055/a-2268-8114
Original Article: Endocrine Care

Association of VEGF+936 C/T Polymorphism with Susceptibility to Type 2 Diabetic Retinopathy: A Meta-Analysis

Yanhong Huo
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, Beijing, China
,
Xin Zhang
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, Beijing, China
,
Li Su
1   Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, Beijing, China
,
Yan Zhang
2   Department of Ophthalmology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
› Author Affiliations
Funding Information Beijing Municipal Science & Technology Commission — Z171100001017163 The Beijing Natural Science Foundation — 7162048

Abstract

The objective of this study is to explore the relationship between the vascular endothelial growth factor (VEGF)+936 C/T polymorphism and the risk of type 2 diabetic retinopathy (T2DR) by a method of meta-analysis. Six online databases were queried to identify studies investigating the VEGF+936 C/T polymorphism that influenced T2DR up to August 2023. The statistical tool of the pooled data was adopted using Stata 15.0 software. The experimental group comprised patients with T2DR, while patients with type 2 diabetes mellitus without retinopathy were considered as the controls. The odds ratio (OR) was utilized as effect size. Eight eligible publications were identified in this review, including 1546 patients with T2DR. The combined results revealed that the VEGF+936 C/T polymorphism was significantly associated with the T2DR risk under the allelic (C/T: OR=0.54, p<0.001), the dominant (CC+CT/TT: OR=0.37, p<0.001), recessive (CC/CT+TT: OR=0.52, p=0.001), homozygous (CC/TT: OR=0.31, p<0.001), and heterozygous (CT/TT: OR=0.55, p=0.005) gene models. No significant correlation was observed regarding the VEGF+936 C/T polymorphism that contributed to the risk of proliferative diabetic retinopathy (PDR) versus non-PDR. In conclusion, the VEGF+936 C/T polymorphism significantly contributed to the T2DR risk. Specifically, at the VEGF+936 C/T locus, the presence of allele C and genotypes CC, CT, and CC+CT were found to be associated with a reduced risk of T2DR.

Supplementary Material



Publication History

Received: 13 September 2023

Accepted: 09 February 2024

Article published online:
12 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013; 93: 137-188
  • 2 Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treatments. Int J Mol Sci 2018; 19: 1816
  • 3 Teo ZL, Tham YC, Yu MCY. et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 2021; 128: 1580-1591
  • 4 Pan CW, Wang S, Qian DJ. et al. Prevalence, awareness, and risk factors of diabetic retinopathy among adults with known type 2 diabetes mellitus in an urban community in China. Ophthal. Epidemiol 2017; 24: 188-194
  • 5 Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010; 376: 124-136
  • 6 Claesson-Welsh L, Welsh M. VEGFA and tumour angiogenesis. J Intern Med 2013; 273: 114-1127
  • 7 Semino CE, Kamm RD, Lauffenburger DA. Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow. Eep Cell Res 2006; 312: 289-298
  • 8 Lahdenranta J, Hagendoorn J, Padera TP. et al. Endothelial nitric oxide synthase mediates lymphangiogenesis and lymphatic metastasis. Cancer Res 2009; 69: 2801-2808
  • 9 Su Y, Zhang X, Zuo C. et al. Three vvariants of or near VEGF-A gene are not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese population. Ophthalmic Genet 2015; 36: 218-223
  • 10 Abdelgalil AA, Monir R, Elmetwally M. et al The relation of VEGFA, VEGFR2, VEGI, and HIF1A genetic variants and their serum protein levels with breast cancer in Egyptian patients. Biochem Genet 2024; 62: 547–573 DOI: 10.1007/s10528-023-10419-4.
  • 11 Wei N, Chen Z, Xue Z. et al. Polymorphism of VEGF gene in susceptibility to chronic immune-mediated inflammatory diseases: a meta-analysis. Rheumatol Int 2015; 35: 1351-1360
  • 12 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 Diabetes Res 2014; DOI: 10.1155/2014/805801.
  • 13 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 2016; 9: 738-753
  • 14 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
  • 15 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
  • 16 Awata T, Inoue K, Kurihara S. et al. A common polymorphism in the 5’-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 2002; 51: 1635-1639
  • 17 Uthra S, Raman R, Mukesh BN. et al. Association of VEGF gene polymorphisms with diabetic retinopathy in a south Indian cohort. Ophthalmic Genet 2008; 29: 11-15
  • 18 Kim HW, Gang JK, Kang YS. et al. Role of the VEGF 936 C/T polymorphism in diabetic microvascular complications in type 2 diabetic patients. Nephrology 2010; 14: 681-688
  • 19 Fan XH, Wu QH, Li Y. et al. Association of polymorphisms in the vascular endothelial growth factor gene and its serum levels with diabetic retinopathy in Chinese patients with type 2 diabetes: a cross-sectional study. Chin Med J-P 2014; 7: 651-657
  • 20 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
  • 21 Choudhuri S, Chowdhury IH, Das S. et al. Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy. Mol Cell Biochem 2015; 405: 265-279
  • 22 Li L, Yi XL, Gu YX. et al. Association of genetic polymorphism of VEGF, ICAM-1 K469E, EPO and TCF7L2 genes with diabetic retinopathy of type 2 diabetes mellitus in Uyghur population in Xinjiang. J Xinjiang Med Univ 2016; 39: 1267-1271
  • 23 Wu QJ, Wu PP, Lu XP. et al. Relationship between VEGF gene polymorphism and diabetic retinopathy in Li Nationality type 2 diabetic patients in Hainan. Int Eye Sci 2022; 22: 322-326
  • 24 Bonfiglio V, Platania CBM, Lazzara F. et al. TGF-β serum levels in diabetic retinopathy patients and the role of anti-VEGF therapy. Int J Mol Sci 2020; 21: 9558
  • 25 Caldwell RB, Bartoli M, Behzadian MA. et al. Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 2005; 6: 511-524
  • 26 Duh E, Yang H, Haller J. et al. Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor: implications for ocular angiogenesis 1. Am J Ophthalmol 2004; 137: 668-674