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Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis

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Abstract

Published data on the association of vascular endothelial growth factor (VEGF) gene polymorphisms with retinopathy of prematurity (ROP) are inconclusive. The aim of the study was to assess the association by using meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, Cochrane Library and China National Knowledge Infrastructure, with the last report up to 30 April, 2012. The odds ratio (OR) and its 95 % confidence interval (95 %CI) were used to assess the strength of the association. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. A total of 7 studies based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for four VEGF gene polymorphisms (−634G/C, −460T/C, −2578C/A and 936C/T). Significant association was found for −460T/C polymorphism (C vs T: OR = 0.74, 95 %CI = 0.57–0.95, P = 0.02; TC+CC vs TT: OR = 0.75, 95 %CI = 0.47–1.21, P = 0.24; CC vs TT+TC: OR = 0.45, 95 %CI = 0.26–0.76, P = 0.003; CC vs TT: OR = 0.45, 95 %CI = 0.24–0.84, P = 0.01; TC vs TT: OR = 0.96, 95 %CI = 0.59–1.57, P = 0.87) in the VEGF gene, but not for other polymorphisms (−634G/C, −2578C/A and 936C/T). This meta-analysis demonstrates that advanced ROP is associated with VEGF gene −460T/C polymorphism, but not −634G/C, −2578C/A and 936C/T.

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References

  1. Ng YK, Fielder AR, Shaw DE, Levene MI (1988) Epidemiology of retinopathy of prematurity. Lancet 2:1235–1238

    Article  PubMed  CAS  Google Scholar 

  2. Patz A, Eastham A, Higginbotham DH, Kleh T (1953) Oxygen studies in retrolental fibroplasia. II. The production of the microscopic changes of retrolental fibroplasia in experimental animals. Am J Ophthalmol 36:1511–1522

    PubMed  CAS  Google Scholar 

  3. Chen ML, Guo L, Smith LE, Dammann CE, Dammann O (2010) High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis. Pediatrics 125:e1483–e1492

    Article  PubMed  Google Scholar 

  4. Gilbert C (2008) Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev 84:77–82

    Article  PubMed  Google Scholar 

  5. Shastry BS (2010) Genetic susceptibility to advanced retinopathy of prematurity (ROP). J Biomed Sci 17:69

    Article  PubMed  Google Scholar 

  6. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME (2008) Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 27:331–371

    Article  PubMed  CAS  Google Scholar 

  7. Pierce EA, Foley ED, Smith LE (1996) Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 114:1219–1228

    Article  PubMed  CAS  Google Scholar 

  8. Vincenti V, Cassano C, Rocchi M, Persico G (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93:1493–1495

    Article  PubMed  CAS  Google Scholar 

  9. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA (1991) The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266:11947–11954

    PubMed  CAS  Google Scholar 

  10. Gismondi D, Ndoja L, Qu X, Shastry BS (2012) Lack of association of VEGF gene 3′- UTR polymorphisms (C702T, C936T and G1612A) and the risk of developing advanced retinopathy of prematurity (ROP). Graefes Arch Clin Exp Ophthalmol. doi:10.1007/s00417-011-1913-4

  11. Kusuda T, Hikino S, Ohga S, Kinjo T, Ochiai M, Takahata Y, Tokunaga S, Ihara K, Hata Y, Hara T (2011) Genetic variation of vascular endothelial growth factor pathway does not correlate with the severity of retinopathy of prematurity. J Perinatol 31:246–250

    Article  PubMed  CAS  Google Scholar 

  12. Shastry BS (2009) Lack of association of VEGF (-2578 C– > A) and ANG 2 (-35 G– > C) gene polymorphisms with the progression of retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 247:859–860

    Article  PubMed  Google Scholar 

  13. Kwinta P, Bik-Multanowski M, Mitkowska Z, Tomasik T, Pietrzyk JJ (2008) The clinical role of vascular endothelial growth factor (VEGF) system in the pathogenesis of retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 246:1467–1475

    Article  PubMed  CAS  Google Scholar 

  14. Shastry BS, Qu X (2007) 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 245:741–743

    Article  PubMed  CAS  Google Scholar 

  15. Bányász I, Bokodi G, Vannay A, Szebeni B, Treszl A, Vásárhelyi B, Tulassay T, Szabó A (2006) Genetic polymorphisms of vascular endothelial growth factor and angiopoietin 2 in retinopathy of prematurity. Curr Eye Res 31:685–690

    Article  PubMed  Google Scholar 

  16. Vannay A, Dunai G, Bányász I, Szabó M, Vámos R, Treszl A, Hajdú J, Tulassay T, Vásárhelyi B (2005) Association of genetic polymorphisms of vascular endothelial growth factor and risk for proliferative retinopathy of prematurity. Pediatr Res 57:396–398

    Article  PubMed  CAS  Google Scholar 

  17. Cooke RW, Drury JA, Mountford R, Clark D (2004) Genetic polymorphisms and retinopathy of prematurity. Invest Ophthalmol Vis Sci 45:1712–1715

    Article  PubMed  Google Scholar 

  18. Munafo MR, Flint J (2004) Meta-analysis of genetic association studies. Trends Genet 20:439–444

    Article  PubMed  CAS  Google Scholar 

  19. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  20. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  21. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  22. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  23. Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Br Med J 315:629–634

    Article  CAS  Google Scholar 

  24. Karna P, Muttineni J, Angell L, Karmaus W (2005) Retinopathy of prematurity and risk factors: a prospective cohort study. BMC Pediatr 5:18

    Article  PubMed  Google Scholar 

  25. Dunai G, Vásárhelyi B, Szabó M, Hajdú J, Mészáros G, Tulassay T, Treszl A (2008) Published genetic variants in retinopathy of prematurity: random forest analysis suggests a negligible contribution to risk and severity. Curr Eye Res 33:501–505

    Article  PubMed  CAS  Google Scholar 

  26. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182

    Article  PubMed  CAS  Google Scholar 

  27. Chen J, Smith LE (2007) Retinopathy of prematurity. Angiogenesis 10:133–140

    Article  PubMed  Google Scholar 

  28. Errera FI, Canani LH, Silva ME, Yeh E, Takahashi W, Santos KG, Souto KE, Tschiedel B, Roisenberg I, Gross JL, Passos-Bueno MR (2007) Functional vascular endothelial growth factor -634G > C SNP is associated with proliferative diabetic retinopathy: a case-control study in a Brazilian population of European ancestry. Diabetes Care 30:275–279

    Article  PubMed  CAS  Google Scholar 

  29. Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tseng SH, Tsai FJ (2008) Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration. Am J Ophthalmol 145:1045–1051

    Article  PubMed  CAS  Google Scholar 

  30. Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  PubMed  CAS  Google Scholar 

  31. Claffey KP, Robinson GS (1996) Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis. Cancer Metastasis Rev 15:165–176

    Article  PubMed  CAS  Google Scholar 

  32. Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL, Pope RM, Ferrara N (1994) Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152:4149–4156

    PubMed  CAS  Google Scholar 

  33. Miller JW, Adamis AP, Aiello LP (1997) Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes Metab Rev 13:37–50

    Article  PubMed  CAS  Google Scholar 

  34. Budd SJ, Hartnett ME (2010) Increased angiogenic factors associated with peripheral avascular retina and intravitreous neovascularization: a model of retinopathy of prematurity. Arch Ophthalmol 128:589–595

    Article  PubMed  CAS  Google Scholar 

  35. Young HS, Summers AM, Read IR, Fairhurst DA, Plant DJ, Campalani E, Smith CH, Barker JN, Detmar MJ, Brenchley PE, Griffiths CE (2006) Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis. J Invest Dermatol 126:453–459

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank all the people who give the help for this study. This work was supported by grants from 2011 Guangdong Province Medical Foundation (A2011550).

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Affiliated Shenzhen Maternity & Child Healthcare Hospital of Southern Medical University, Shenzhen, 518028, China

    Peihui Liu, Yawen Li, Chaohui Lian & Yueping Yang

  2. Department of Pediatrics, BaYi Children’s Hospital Affiliated to BaYi Clinical Medical College of Southern Medical University, Peking, 100700, China

    Peihui Liu, Weiqin Zhou & Zhichun Feng

  3. Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    De Wu

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  1. Peihui Liu
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  2. De Wu
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Correspondence to Zhichun Feng.

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Liu, P., Wu, D., Zhou, W. et al. Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis. Mol Biol Rep 39, 10731–10737 (2012). https://doi.org/10.1007/s11033-012-1964-6

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  • DOI: https://doi.org/10.1007/s11033-012-1964-6

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