Association between eNOS Gene a/b Polymorphism and Diabetic Retinopathy Susceptibility: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 ZENGZheng-hong , ZHONGLi , WANGMin , LEIChun-li

、Department of Endocrinology Medicine, The First Peoples' Hospital of Longquanyi District, Chengdu 610100, China;

Corresponding?author：

Keywords：

eNOS; Diabetic retinopathy; Polymorphism; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20150152

Video：

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Objective To systematically evaluate the association between eNOS gene a/b polymorphism and diabetic retinopathy susceptibility. Methods PubMed, EMbase, The Cochrane Library (Issue 5, 2015), CBM, CNKI, VIP and WanFang Data were systemically searched from inception to May 2015, to collect case-control studies about the eNOS a/b polymorphism and diabetic retinopathy susceptibility. Two reviewers independently screened literature, extracted data and evaluated the risk bias of included studies. Then, meta-analysis was performed by RevMan 5.2 software. Results A total of 16 case-control studies were included, which involved 3 232 diabetic retinopathy cases and 3 555 controls. The results of meta-analysis showed that, in the total analysis, the a/b polymorphism of the eNOS gene was not associated with diabetic retinopathy risk (dominant model:OR=0.94, 95%CI 0.78 to 1.15, P=0.57; recessive model:OR=0.97, 95%CI 0.78 to 1.22, P=0.88; aa vs. bb:OR=0.89, 95%CI 0.71 to 1.12, P=0.32; ab vs. bb:OR=0. 94, 95%CI 0.77 to 1.14, P=0.52; a vs. b:OR=0.97, 95%CI 0.82 to 1.14, P=0.70); In the subgroup analysis by ethnicity, the a/b polymorphism was significantly associated with the risk of diabetic retinopathy in Africans, but not in Asians and Caucasians. Conclusion The a/b polymorphism in the eNOS gene may be a risk factor of diabetic retinopathy in Africans.

Citation： ZENGZheng-hong, ZHONGLi, WANGMin, LEIChun-li. Association between eNOS Gene a/b Polymorphism and Diabetic Retinopathy Susceptibility: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(8): 898-906. doi: 10.7507/1672-2531.20150152 Copy

1.	Hsieh YY, Huang YC, Chang CC, et al. Chromosome 15q21-22-related polymorphisms and haplotypes are associated with susceptibility to type-2 diabetic nonproliferative retinopathy. Genet Test Mol Biomarkers, 2012, 16(5):442-448.
2.	Lu Y, Ge Y, Hu Q, et al. Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population. J Renin Angiotensin Aldosterone Syst, 2012, 13(2):289-295.
3.	Paine SK, Sen A, Choudhuri S, et al. Association of tumor necrosis factor alpha, interleukin 6, and interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects. Retina, 2012, 32(6):1197-1203.
4.	Okumus S, Igci YZ, Taskin T, et al. Association between Thr21Met and Ser89Asn polymorphisms of the urotensin-Ⅱ (UTS2) gene, diabetes mellitus, and diabetic retinopathy. Curr Eye Res, 2012, 37(10):921-929.
5.	Hu C, Zhang R, Yu W, et al. CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. Diabetes, 2011, 60(11):3085-3089.
6.	Niu W, Qi Y. An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy. Diabetes Res Clin Pract, 2012, 95(1):110-118.
7.	Arden GB, Sivaprasad S. The pathogenesis of early retinal changes of diabetic retinopathy. Doc Ophthalmol, 2012, 124(1):15-26.
8.	Kang P, Tian C, Jia C. Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy. Gene, 2012, 500(1):1-9.
9.	de Syllos RW, Sandrim VC, Lisboa HR, et al. Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients. Nitric Oxide, 2006, 15(4):417-422.
10.	Santos KG, Crispim D, Canani LH, et al. Relationship of endothelial nitric oxide synthase (eNOS) gene polymorphisms with diabetic retinopathy in Caucasians with type 2 diabetes. Ophthalmic Genet, 2012, 33(1):23-27.
11.	孫海燕, 楊明功, 劉樹琴, 等. 內皮型一氧化氮合酶基因多態性與 2 型糖尿病及視網膜病變. 中華內分泌代謝雜志, 2004, 20(1):52-53.
12.	張敏, 劉華, 徐玉善, 等. 2型糖尿病患者eNOS基因第4內含子的多態性與糖尿病視網膜病相關性. 中華內分泌代謝雜志, 2005, 21(2):146-147.
13.	岳枚, 喻曉兵, 戴虹, 等. 內皮型一氧化氮合酶基因第4內含子中27堿基對重復序列多態性與糖尿病視網膜病變的相關性研究. 中華眼底病雜志, 2011, 27(3):214-217.
14.	Cheema BS, kohli HS, Sharma R, et al. Endothelial nitric oxide synthase gene polymorphism and type 2 diabetic retinopathy among Asian Indians. Acta Diabetol, 2012, 49(6):481-488.
15.	Ezzidi I, Mtiraoui N, Mohamed MB, et al. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and T-786C polymorphisms in type 2 diabetic retinopathy. Clin Endocrinol (Oxf), 2008, 68(4):542-546.
16.	Awata T, Neda T, Iizuka H, et al. Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes. Diabetes Care, 2004, 27(9):2184-2190.
17.	Mehrab-Mohseni M, Tabatabaei-Malazy O, Hasani-Ranjbar S, et al. Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with type 2 diabetes and its chronic complications. Diabetes Res Clin Pract, 2011, 91(3):348-352.
18.	Petrovic MG, Cilensek I, Petrovic D. Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients. Dis Markers, 2008, 24(1):59-64.
19.	Cilensek I, Mankoc S, Globocnik Petrovic M, et al. The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients (Caucasians) with type 2 diabetes mellitus. Mol Biol Rep, 2012, 39(6):7061-7067.
20.	Chen Y, Huang H, Zhou J, et al. Polymorphism of the endothelial nitric oxide synthase gene is associated with diabetic retinopathy in a cohort of West Africans. Mol Vis, 2007, 13:2142-2147.
21.	Suganthalakshmi B, Anand R, Kim R, et al. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis, 2006, 12:336-341.
22.	Narne P, Ponnaluri KC, Siraj M, et al. Association Analysis of Polymorphisms in Genes Related to Oxidative Stress in South Indian Type 2 Diabetic Patients with Retinopathy. Ophthalmic Genet, 2014:in press.
23.	佘重陽, 楊秀芬, 顧虹, 等. 內皮型一氧化氮合酶基因內含子的數目可變串聯重復多態性與糖尿病視網膜病變的相關性研究. 中華眼科雜志, 2015, 51(5):338-343.
24.	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(9):603-605.
25.	陳甲, 和儒林, 朗瑩, 等. 中國人群MTHFR基因C677T多態性與青中年缺血性腦卒中相關性的Meta分析. 中國循證醫學雜志, 2014, 14(4):435-442.
26.	Qian-Qian Y, Yong Y, Jing Z, et al. Association between a 27-bp variable number of tandem repeat polymorphism in intron 4 of the eNOS gene and risk for diabetic retinopathy Type 2 diabetes mellitus:a meta-analysis. Curr Eye Res, 2014, 39(10):1052-1058.

1. Hsieh YY, Huang YC, Chang CC, et al. Chromosome 15q21-22-related polymorphisms and haplotypes are associated with susceptibility to type-2 diabetic nonproliferative retinopathy. Genet Test Mol Biomarkers, 2012, 16(5):442-448.
2. Lu Y, Ge Y, Hu Q, et al. Association between angiotensin-converting enzyme gene polymorphism and diabetic retinopathy in the Chinese population. J Renin Angiotensin Aldosterone Syst, 2012, 13(2):289-295.
3. Paine SK, Sen A, Choudhuri S, et al. Association of tumor necrosis factor alpha, interleukin 6, and interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects. Retina, 2012, 32(6):1197-1203.
4. Okumus S, Igci YZ, Taskin T, et al. Association between Thr21Met and Ser89Asn polymorphisms of the urotensin-Ⅱ (UTS2) gene, diabetes mellitus, and diabetic retinopathy. Curr Eye Res, 2012, 37(10):921-929.
5. Hu C, Zhang R, Yu W, et al. CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients. Diabetes, 2011, 60(11):3085-3089.
6. Niu W, Qi Y. An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy. Diabetes Res Clin Pract, 2012, 95(1):110-118.
7. Arden GB, Sivaprasad S. The pathogenesis of early retinal changes of diabetic retinopathy. Doc Ophthalmol, 2012, 124(1):15-26.
8. Kang P, Tian C, Jia C. Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy. Gene, 2012, 500(1):1-9.
9. de Syllos RW, Sandrim VC, Lisboa HR, et al. Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients. Nitric Oxide, 2006, 15(4):417-422.
10. Santos KG, Crispim D, Canani LH, et al. Relationship of endothelial nitric oxide synthase (eNOS) gene polymorphisms with diabetic retinopathy in Caucasians with type 2 diabetes. Ophthalmic Genet, 2012, 33(1):23-27.
11. 孫海燕, 楊明功, 劉樹琴, 等. 內皮型一氧化氮合酶基因多態性與 2 型糖尿病及視網膜病變. 中華內分泌代謝雜志, 2004, 20(1):52-53.
12. 張敏, 劉華, 徐玉善, 等. 2型糖尿病患者eNOS基因第4內含子的多態性與糖尿病視網膜病相關性. 中華內分泌代謝雜志, 2005, 21(2):146-147.
13. 岳枚, 喻曉兵, 戴虹, 等. 內皮型一氧化氮合酶基因第4內含子中27堿基對重復序列多態性與糖尿病視網膜病變的相關性研究. 中華眼底病雜志, 2011, 27(3):214-217.
14. Cheema BS, kohli HS, Sharma R, et al. Endothelial nitric oxide synthase gene polymorphism and type 2 diabetic retinopathy among Asian Indians. Acta Diabetol, 2012, 49(6):481-488.
15. Ezzidi I, Mtiraoui N, Mohamed MB, et al. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and T-786C polymorphisms in type 2 diabetic retinopathy. Clin Endocrinol (Oxf), 2008, 68(4):542-546.
16. Awata T, Neda T, Iizuka H, et al. Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes. Diabetes Care, 2004, 27(9):2184-2190.
17. Mehrab-Mohseni M, Tabatabaei-Malazy O, Hasani-Ranjbar S, et al. Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with type 2 diabetes and its chronic complications. Diabetes Res Clin Pract, 2011, 91(3):348-352.
18. Petrovic MG, Cilensek I, Petrovic D. Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients. Dis Markers, 2008, 24(1):59-64.
19. Cilensek I, Mankoc S, Globocnik Petrovic M, et al. The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients (Caucasians) with type 2 diabetes mellitus. Mol Biol Rep, 2012, 39(6):7061-7067.
20. Chen Y, Huang H, Zhou J, et al. Polymorphism of the endothelial nitric oxide synthase gene is associated with diabetic retinopathy in a cohort of West Africans. Mol Vis, 2007, 13:2142-2147.
21. Suganthalakshmi B, Anand R, Kim R, et al. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis, 2006, 12:336-341.
22. Narne P, Ponnaluri KC, Siraj M, et al. Association Analysis of Polymorphisms in Genes Related to Oxidative Stress in South Indian Type 2 Diabetic Patients with Retinopathy. Ophthalmic Genet, 2014:in press.
23. 佘重陽, 楊秀芬, 顧虹, 等. 內皮型一氧化氮合酶基因內含子的數目可變串聯重復多態性與糖尿病視網膜病變的相關性研究. 中華眼科雜志, 2015, 51(5):338-343.
24. 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(9):603-605.
25. 陳甲, 和儒林, 朗瑩, 等. 中國人群MTHFR基因C677T多態性與青中年缺血性腦卒中相關性的Meta分析. 中國循證醫學雜志, 2014, 14(4):435-442.
26. Qian-Qian Y, Yong Y, Jing Z, et al. Association between a 27-bp variable number of tandem repeat polymorphism in intron 4 of the eNOS gene and risk for diabetic retinopathy Type 2 diabetes mellitus:a meta-analysis. Curr Eye Res, 2014, 39(10):1052-1058.

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Association between eNOS Gene a/b Polymorphism and Diabetic Retinopathy Susceptibility: A Meta-analysis

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