Association of vascular endothelial growth factor gene polymorphism with diabetic retinopathy in different population: a meta-analysis_Chinese Journal of Ocular Fundus Diseases

Authors：

GuoLu ,  LyuHongbin

Department of Ophthalmology, The Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China;

Corresponding author：

LyuHongbin, Email: oculistlvhongbin@163.com

Keywords：

Diabetic retinopathy/etiology; Genetic pleiotropy; Vascular endothelial growth Factors; Meta-analysis

DOI：

10.3760/cma.j.issn.1005-1015.2015.02.016

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Objective To assess the association of vascular endothelial growth factor (VEGF) gene-460C/T and-634C/G polymorphism with diabetic retinopathy (DR) among patients in Asia and European by meta-analysis. Methods A systematic search of electronic databases (PubMed, Cochrane Library, EMBASE, VIP, Wanfang technological, CNKI, etc.) was carried out until Jun, 2014. Case-control studies on the relationship between genetic polymorphism of VEGF-460C/T and VEGF-634C/G with diabetic retinopathy were included in this analysis. The data were quantitatively analyzed by RevMan 5.0 software after assessing the quality of included studies. The pooled odds ratios (OR) and their corresponding 95% confidence intervals (CI) were used to assess the strength of the association. Results VEGF-460C/T (7 studies:899 cases and 786 controls) and VEGF-634C/G (10 studies:1615 cases and 1861 controls) were inclued in this meta-analysis. Significant association was found for-460C/T polymorphism in Aisa (C versus T:OR=1.52, 95%CI was, Z=3.72, P=0.0002; CC versus CT+TT:OR=1.61, 95%CI was[1.22, 1.90], Z=3.05, P=0.002; TT versus CT+CC:OR=0.64, 95%CI was[1.19, 2.19], Z=2.07, P=0.04), and VEGF-634CC gene type was associated with DR in European (OR=1.56, 95%CI[1.08, 2.25], Z=2.37, P=0.02). No significant publication bias was found. Conclusions The meta-analysis demonstrated that DR was associated with VEGF-460C/T polymorphism in Asia, and C alleles and CC gene type was the risk polymorphism; VEGF-634C/G polymorphism was not associated with DR, but its CC genotype maybe the risk factor in European. Further case-control studies based on larger sample size are still needed, especially for-634C/G polymorphism.

Citation： GuoLu, LyuHongbin. Association of vascular endothelial growth factor gene polymorphism with diabetic retinopathy in different population: a meta-analysis. Chinese Journal of Ocular Fundus Diseases, 2015, 31(2): 173-178. doi: 10.3760/cma.j.issn.1005-1015.2015.02.016 Copy

1.	Patel S, Chen H, Tinkham NH, et al. Genetic susceptibility of diabetic retinopathy[J].Curr Diab Rep, 2008, 8(4):257-262.
2.	Wirostko B, Wong TY, Simo R. Vascular endothelial growth factor and diabetic complications[J]. Prog Retin Eye Res, 2008, 27(6):608-621.
3.	Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins[J].Proc Natl Acad Sci USA, 1995, 92(23):10457-10461.
4.	Stevens A, Soden J, Brenchley PE, et al. Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter[J]. Cancer Res, 2003, 63(4):812-816.
5.	Yang X, Deng Y, Gu H. Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes[J]. Mol Vis, 2011, 17:3088-3096.
6.	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[J]. Diabetes, 2002, 51(5):1635-1639.
7.	Suganthalakshmi B, Anand R, Kim R, et al.Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy[J].Mol Vis, 2006, 12:336-341.
8.	Szaflik JP, Wysocki T, Kowalski M, et al.An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy[J].Graefe's Arch Clin Exp Ophthalmol, 2008, 246(1):39-43.
9.	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[J]. Mol Vis, 2012, 18:2749-2757.
10.	Ray D, Mishra M, Ralph S, et al. Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes[J]. Diabetes, 2004. 53(3):861-864.
11.	何皓, 李传辉, 金成吉.血管内皮生长因子基因多态性与糖尿病视网膜病变相关性研究[J].中国老年学杂志, 2009, 29(3):347-348.
12.	王晓梅, 成吉, 杨晓辉, 等.血管内皮生长因子基因多态性与糖尿病视网膜病变的相关性[J].中国糖尿病杂志, 2008, 16(8):462-464.
13.	杨磊.VEGF和PEDF的基因多态性与增殖型糖尿病视网膜病变的关系.石家庄:河北医科大学, 2009.
14.	郑薇.血管内皮生长因子基因多态性和糖尿病视网膜病变的关系.湖南衡阳:南华大学, 2006.
15.	Awata T, Kurihara S, Takata N, et al. Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and correlated with macular retinal thickness in type 2 diabetes[J]. Biochem Biophys Res Commun, 2005, 333(3):6679-6685.
16.	Chun MY, Hwang HS, Cho HY, et al. Association of vascular endothelial growth factor polymorphisms with nonproliferative and proliferative diabetic retinopathy[J]. J Clin Endocrinol Metab, 2010, 95(7):3547-3551.
17.	Nakamura S, Iwasaki N, Funatsu H, et al. Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2009, 247(1):21-26.
18.	Uthra S, Raman R, Mukesh BN, et al. Association of VEGF gene polymorphisms with diabetic retinopathy in a south Indian cohort[J]. Ophthalmic Genet, 2008, 29(1):11-15.
19.	Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, et al. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients[J]. Nephrol Dial Transplant, 2007, 22(3):827-832.
20.	Errera FI, Canani LH, Silva ME, et al.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[J]. Diabetes Care, 2007, 30(2):275-279.
21.	Feghhi M, Nikzamir A, Esteghamati A, et al. Relationship of vascular endothelial growth factor (VEGF) 1405 G/C polymorphism and proliferative retinopathy in patients with type 2 diabetes[J].Transl Res, 2011, 158(2):85-91.
22.	Petrovic MG, Korosec P, Kosnik M, et al. Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy[J]. Mol Vis, 2008, 14:1382-1387.
23.	Kangas-Kontio T, Vavuli S, Kakko SJ, et al. Polymorphism of the manganese superoxide dismutase gene but not of vascular endothelial growth factor gene is a risk factor for diabetic retinopathy[J]. Br J Ophthalmol, 2009, 93(10):1401-1406.
24.	Yang Y, Andresen BT, Yang K, et al. Association of vascular endothelial growth factor 2634C/G polymorphism and diabetic retinopathy in type 2 diabetic Han Chinese[J]. Exp Biol Med, 2010, 235(10):1204-1211.
25.	Al-Kateb H, Mirea L, Xie X, et al. Multiple variants in vascular endothelial growth factor (VEGFA) are risk factors for time to severe retinopathy in type 1 diabetes:the DCCT/EDIC genetics study[J]. Diabetes, 2007, 56(8):2161-2168.

1. Patel S, Chen H, Tinkham NH, et al. Genetic susceptibility of diabetic retinopathy[J].Curr Diab Rep, 2008, 8(4):257-262.
2. Wirostko B, Wong TY, Simo R. Vascular endothelial growth factor and diabetic complications[J]. Prog Retin Eye Res, 2008, 27(6):608-621.
3. Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins[J].Proc Natl Acad Sci USA, 1995, 92(23):10457-10461.
4. Stevens A, Soden J, Brenchley PE, et al. Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter[J]. Cancer Res, 2003, 63(4):812-816.
5. Yang X, Deng Y, Gu H. Polymorphisms in the vascular endothelial growth factor gene and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes[J]. Mol Vis, 2011, 17:3088-3096.
6. 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[J]. Diabetes, 2002, 51(5):1635-1639.
7. Suganthalakshmi B, Anand R, Kim R, et al.Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy[J].Mol Vis, 2006, 12:336-341.
8. Szaflik JP, Wysocki T, Kowalski M, et al.An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy[J].Graefe's Arch Clin Exp Ophthalmol, 2008, 246(1):39-43.
9. 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[J]. Mol Vis, 2012, 18:2749-2757.
10. Ray D, Mishra M, Ralph S, et al. Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes[J]. Diabetes, 2004. 53(3):861-864.
11. 何皓, 李传辉, 金成吉.血管内皮生长因子基因多态性与糖尿病视网膜病变相关性研究[J].中国老年学杂志, 2009, 29(3):347-348.
12. 王晓梅, 成吉, 杨晓辉, 等.血管内皮生长因子基因多态性与糖尿病视网膜病变的相关性[J].中国糖尿病杂志, 2008, 16(8):462-464.
13. 杨磊.VEGF和PEDF的基因多态性与增殖型糖尿病视网膜病变的关系.石家庄:河北医科大学, 2009.
14. 郑薇.血管内皮生长因子基因多态性和糖尿病视网膜病变的关系.湖南衡阳:南华大学, 2006.
15. Awata T, Kurihara S, Takata N, et al. Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and correlated with macular retinal thickness in type 2 diabetes[J]. Biochem Biophys Res Commun, 2005, 333(3):6679-6685.
16. Chun MY, Hwang HS, Cho HY, et al. Association of vascular endothelial growth factor polymorphisms with nonproliferative and proliferative diabetic retinopathy[J]. J Clin Endocrinol Metab, 2010, 95(7):3547-3551.
17. Nakamura S, Iwasaki N, Funatsu H, et al. Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2009, 247(1):21-26.
18. Uthra S, Raman R, Mukesh BN, et al. Association of VEGF gene polymorphisms with diabetic retinopathy in a south Indian cohort[J]. Ophthalmic Genet, 2008, 29(1):11-15.
19. Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, et al. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients[J]. Nephrol Dial Transplant, 2007, 22(3):827-832.
20. Errera FI, Canani LH, Silva ME, et al.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[J]. Diabetes Care, 2007, 30(2):275-279.
21. Feghhi M, Nikzamir A, Esteghamati A, et al. Relationship of vascular endothelial growth factor (VEGF) 1405 G/C polymorphism and proliferative retinopathy in patients with type 2 diabetes[J].Transl Res, 2011, 158(2):85-91.
22. Petrovic MG, Korosec P, Kosnik M, et al. Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy[J]. Mol Vis, 2008, 14:1382-1387.
23. Kangas-Kontio T, Vavuli S, Kakko SJ, et al. Polymorphism of the manganese superoxide dismutase gene but not of vascular endothelial growth factor gene is a risk factor for diabetic retinopathy[J]. Br J Ophthalmol, 2009, 93(10):1401-1406.
24. Yang Y, Andresen BT, Yang K, et al. Association of vascular endothelial growth factor 2634C/G polymorphism and diabetic retinopathy in type 2 diabetic Han Chinese[J]. Exp Biol Med, 2010, 235(10):1204-1211.
25. Al-Kateb H, Mirea L, Xie X, et al. Multiple variants in vascular endothelial growth factor (VEGFA) are risk factors for time to severe retinopathy in type 1 diabetes:the DCCT/EDIC genetics study[J]. Diabetes, 2007, 56(8):2161-2168.

Chinese Journal of Ocular Fundus Diseases

Association of vascular endothelial growth factor gene polymorphism with diabetic retinopathy in different population: a meta-analysis

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