Association of -634 C/G Polymorphism at Vascular Endothelial Growth Factor Gene with Risk Retinopathy of Prematurity

Document Type : Original Article

Authors

1 Department of Advanced Medical Sciences and Technologies, Islamic Azad University, Science and Research Branch, Tehran, Iran

2 Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Department of Pediatrics, Iranshahr University of Medical Sciences, Iranshahr, Iran

4 Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

6 Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: Retinopathy of prematurity (ROP) is a major cause of blindness in newborn infants worldwide. It is well known that neovascularization of the retina is prominent in the proliferative stages of ROP. It is suggested that vascular endothelial growth factor (VEGF) may play a role in the development of ROP. The aim of this study was to evaluate the association of the VEGF -634C/G polymorphism at VEGF with risk of ROP.
Methods: In the study 54 neonates diagnosed with ROP and 55 healthy neonates served as controls. The VEGF -634 C/G polymorphism was genotyped by restriction fragment length polymorphism (PCR-RFLP) technique.
Results: The CC, CG, and GG genotypes of VEGF -634C/G polymorphism were found in 33.3%, 38.9%, and 27.8% of neonates with ROP, respectively. In controls, CC, CG, and GG genotypes were seen in 43.6%, 45.4%, and 10.9%, respectively. Frequency of mutant allele (C) was 52.8% in neonates with ROP and 66.4% in healthy neonates. There was a significant difference in the distribution of VEGF -634C/G polymorphisms between cases and controls. Moreover, there was a significant association between VEGF -634C/G polymorphisms and ROP risk (OR = 3.141, 95% CI 1.115-8.851, P = 0.030).
Conclusion: This study results revealed that VEGF -634C/G polymorphism might serve as a risk factor for development of ROP. Thus, clinicians should be aware of the ROP risk in infant with the VEGF -634C/G polymorphism and ROP risk in infants. However, large sample size and well-designed studies are necessary to validate our findings.

Keywords


  1. Gohari M, Bahrami R, Dastgheib SA, Lookzadeh MH, Noorishadkam M, Mirjalili SR, et al. An updated and comprehensive meta-analysis of association between VEGA -634G > C, -460T > C, +405G > C and +936C > T polymorphisms and retinopathy of prematurity risk. Fetal and Pediatric Pathology 2019.
  2. Gohari M, Dastgheib SAR, Noorishadkam M, Lookzadeh MH, Mirjalili SR, Akbarian-Bafghi MJ, et al. Association of eNOS and ACE Polymorphisms with Retinopathy of Prematurity: A Systematic Review and Meta-Analysis. Fetal Pediatr Pathol 2020; 39(4): 334-45.
  3. Jefferies AL, Canadian Paediatric Society, Fetus and Newborn Committee. Retinopathy of prematurity: An update on screening and management. Paediatr Child Health 2016; 21(2): 101-8.
  4. Port AD, Chan RVP, Ostmo S, Choi D, Chiang MF. Risk factors for retinopathy of prematurity: insights from outlier infants. Graefes Arch Clin Exp Ophthal 2014; 252(10): 1669-77.
  5. Coats DK. Retinopathy of prematurity: Involution, factors predisposing to retinal detachment, and expected utility of preemptive surgical reintervention. Trans Am Ophthalmol Soc 2005; 103: 281-312.
  6. Warren CC, Young JB, Goldberg MR, Connor TB, Kassem IS, Costakos DM. Findings in persistent retinopathy of prematurity. Ophthalmic Surg Lasers Imaging Retina 2018; 49(7): 497-503.
  7. Ortega-Molina JM, Solans-Perez de Larraya A, Salgado-Miranda A, Jerez-Calero A, Uberos-Fernandez J, Gonzalez Ramirez AR, et al. Risk factors of retinopathy of prematurity associated with delayed retinal vascular development. Iran J Pediatr 2017; 27(4): e7642.
  8. Chang JW. Risk factor analysis for the development and progression of retinopathy of prematurity. PLoS One, 2019; 14(7): e0219934.
  9. Hakeem AHAA, Mohamed GB, Othman MF. Retinopathy of prematurity: A study of prevalence and risk factors. Middle East Afr J Ophthalmol 2012; 19(3): 289-94.
  10. Bányász I, Bokodi G, Vannay A, Szebeni B, Treszl A, Vásárhelyi B, et al. Genetic polymorphisms of vascular endothelial growth factor and angiopoietin 2 in retinopathy of prematurity. Curr Eye Res 2006, 31(7-8):
    685-90.
  11. Ortega-Molina JM, Anaya-Alaminos R, Uberos-Fernández J, De Larraya ASP, Chaves-Samaniego MJ, Salgado-Miranda A, et al. Genetic and environmental influences on retinopathy of prematurity. Mediators Inflamm 2015; 2015: 764159.
  12. Kalmeh ZA, Azarpira N, Mosallaei M, Hosseini H, Malekpour Z. Genetic polymorphisms of vascular endothelial growth factor and risk for retinopathy of prematurity in South of Iran. Mol Biol Rep 2013; 40(7): 4613-8.
  13. Cooke RWI, Drury JA, Mountford R, Clark D. Genetic polymorphisms and retinopathy of prematurity. Invest Ophthalmol Vis Sci 2004; 45(6): 1712-5.
  14. Poggi C, Giusti B, Gozzini E, Sereni A, Romagnuolo I, Kura A, et al. Genetic contributions to the development of complications in preterm newborns. PLoS One 2015; 10(7): e0131741.
  15. Swan R, Kim SJ, Campbell JP, Chan RVP, Sonmez K, Taylor KD, et al. The Genetics of Retinopathy of Prematurity: A Model for Neovascular Retinal Disease. Ophthalmol Retina 2018; 2(9): 949-62.
  16. Pozarowska D, Pozarowski P. The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy. Cent Eur J Immunol 2016; 41(3): 311-6.
  17. Hartnett ME. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity. Clin Perinatol 2014; 41(4): 925-43.
  18. Hashemi M, Danesh H, Bizhani F, Mokhtari M, Bahari G, Tabasi F, et al. The -2549 insertion/deletion polymorphism in the promoter region of VEGF is associated with the risk of recurrent spontaneous abortion. Biomedical Reports 2018; 8(3): 297-300.
  19. Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer 2011; 2(12): 1097-105.
  20. Holmes DIR, Zachary I. The vascular endothelial growth factor (VEGF) family: Angiogenic factors in health and disease. Genome Biol 2005; 6(2): 209.
  21. Ali AA, Hussien NF, Samy RM, Al Husseiny K. Polymorphisms of vascular endothelial growth factor and retinopathy of prematurity. Journal of Pediatric Ophthalmology and Strabismus, 2015; 52(4): 245-53.
  22. Lei XJ, Zhao YX, Qiao T. Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants. Int J Ophthal 2018; 11(9): 1451-7.
  23. Kwinta P, Bik-Multanowski M, Mitkowska Z, Tomasik T, Pietrzyk JJ. The clinical role of vascular endothelial growth factor (VEGF) system in the pathogenesis of retinopathy of prematurity. Graefe’s Arch Clin Exp Ophthal
    2008; 246(10): 1467-75. 
  24. Kusuda T, Hikino S, Ohga S, Kinjo T, Ochiai M, Takahata Y, et al. Genetic variation of vascular endothelial growth factor pathway does not correlate with the severity of retinopathy of prematurity. J Perinatol 2011; 31(4): 246-50.
  25. Malik MA, Shukla S, Azad SV, Kaur J. Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis. Saudi J Ophthalmol 2014; 28(4): 299-303.
  26. Luo Y, Tan Y, Wang X. Influence of polymorphisms in VEGF, TNF-α, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis. J Matern Fetal Neonatal Med 2020; 1-10.
  27. Shukla S, Malik MA, Chandra P, Kaur J. Association between VEGF polymorphisms (-460 T/C and +936 C/T) and retinopathy of prematurity risk: A meta-analysis. Saudi J Ophthalmol 2016; 30(3): 157-62.
  28. Shastry BS, Qu X. Lack of association of the VEGF gene promoter (-634 G→C and -460 C→T) polymorphism and the risk of advanced retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2007; 245(5): 741-3.
  29. Liu P, Wu D, Zhou W, Li Y, Lian C, Yang Y, et al. Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis. Mol Biol Rep 2012; 39(12): 10731-7.