Association of -429T/C and G1704 polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

WeiWenwen , FanWenying , WuPeibei , YangXiufen , MaKai ,  LiuNingpu

Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;

Corresponding author：

LiuNingpu, Email: nliu001@gmail.com

Keywords：

Diabetic retinopathy/etiology; Diabetic retinopathy/genetics; Glycosylation end products, advanced/genetics; Polymorphism, genetic

DOI：

10.3760/cma.j.issn.1005-1015.2016.02.005

Video：

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Objective To determine the association of -429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR). Methods Case-control study. From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),atotal of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR, duration of diabetes 15 years) were included for this study. Questionnaires were collected and general ophthalmologic examinations were performed. Biochemical analysis was conducted. DNA was extracted from peripheral venous blood. The -429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms. Results The frequency distribution of -429T/C in DWR group was 81.0% in TT, 16.1% in TC, 2.9% in CC. The frequency distribution of -429T/C in PDR group was 77.3% in TT, 20.6% in TC, 2.1% in CC. There was no significant statistical difference between the two groups (χ²=0.40, P > 0.05). Frequency of the -429T/C minor alleleCin the DWR and PDR group were 11.0% and 12.4%, respectively, with no significant statistical difference between the two groups (χ²=0.20，P > 0.05). The frequency distribution of G1704T in DWR group was 66.7% in GG, 29.5% in GT, 3.8% in TT. The frequency distribution of G1704T in PDR group was 78.4% in GG, 21.6% in GT. There was no significant statistical difference between the two groups (χ²=3.44, P > 0.05). Frequency of the G1704T minor alleleTin the DWR and PDR group were 18.6% and 10.8%, respectively, in which significant difference was found within the two groups (χ²=4.79, OR=1.88，95%CI: 1.06 - 3.33, P > 0.05). Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.

Citation： WeiWenwen, FanWenying, WuPeibei, YangXiufen, MaKai, LiuNingpu. Association of -429T/C and G1704 polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2016, 32(2): 130-134. doi: 10.3760/cma.j.issn.1005-1015.2016.02.005 Copy

1.	Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications[J]. N Engl J Med, 1988, 318(20): 1315-1321. DOI: 10.1056/NEJM198805193182007.
2.	Barile GR, Pachydaki SI, Tari SR, et al. The RAGE axis in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2005, 46(8): 2916-2924. DOI:10.1167/iovs.04-1409.
3.	Yamagishi S, Maeda S, Matsui T, et al. Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes[J]. Biochim Biophys Acta, 2012, 1820(5): 663-671.DOI: 10.1016/j.bbagen.2011.03.014.
4.	Ng ZX, Kuppusamy UR, Tajunisah I, et al. Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy[J]. Diabetes Res Clin Pract, 2012, 95(3): 372-377. DOI: 10.1016/j.diabres.2011.11.005.
5.	Ramprasad S, Radha V, Mathias RA, et al. Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India[J]. Eye (Lond), 2007, 21(3): 395-401. DOI:10.1038/sj.eye.6702239.
6.	Tripathi AK, Chawla D, Bansal S, et al. Association of RAGE gene polymorphism with vascular complications in Indian type 2 diabetes mellitus patients[J]. Diabetes Res Clin Pract, 2014, 103(3): 474-481. DOI: 10.1016/j.diabres.2013.12.004.
7.	Vanita V. Association of RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms with diabetic retinopathy in T2DM patients from north India[J]. Diabetes Res Clin Pract, 2014, 104(1): 155-162. DOI: 10.1016/j.diabres.2013.12.059.
8.	顾喆瑶, 姚勇, 谢田华, 等. 无锡地区汉族人群RAGE基因启动子区-374T/A多态性与糖尿病视网膜病变的相关研究[J]. 眼科新进展, 2014, 34(7): 655-657,661. DOI:10.13389/j.cnki.rao.2014.0179.Gu ZY, Yao Y, Xie TH, et al. Association analysis of advanced glycation end products gene receptor-374T/A poly-morphisms in Han people of Wuxi area with type 2 diabetic retinopathy[J]. Rec Adv Ophthalmol, 2014, 34(7): 655-657,661. DOI:10.13389/j.cnki.rao.2014.0179.
9.	Zhang HM, Chen LL, Wang L, et al. Association of 1704G/T and G82S polymorphisms in the receptor for advanced glycation end products gene with diabetic retinopathy in Chinese population[J]. J Endocrinol Invest, 2009, 32(3): 258-262.
10.	Yang L, Wu Q, Li Y, et al. Association of the receptor for advanced glycation end products gene polymorphisms and circulating RAGE levels with diabetic retinopathy in the Chinese population[J/OL]. J Diabetes Res, 2013, 2013: 264579[2013-11-04]. http://dx.doi.org/10.1155/2013/264579.
11.	李娜, 杨秀芬, 邓禹, 等. 2型糖尿病患者自我管理水平与糖尿病视网膜病变的相关性研究[J].中华眼科杂志, 2013, 49(6): 500-506. DOI: 10.3760/cma.j.issn.0412-4081.2013.06.007.Li N, Yang XF, Deng Y, et al. Diabetes self-management and its association with diabetic retinopathy in patients with type 2 diabetes[J]. Chin J Ophthalmol, 2013, 49(6): 500-506. DOI: 10.3760/cma.j.issn.0412-4081.2013.06.007.
12.	Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10[J]. Ophthalmology, 1991, 98 Suppl 5 : S786-806.
13.	Yang X, Deng Y, Gu H, et al. 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.
14.	Hudson BI, Stickland MH, Futers TS, et al. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy[J]. Diabetes, 2001, 50(6): 1505-1511. DOI: 10.2337/diabetes.50.6.1505.
15.	徐积兄, 徐碧林, 杨明功, 等. RAGE基因启动区-429T/C多态与2型糖尿病肾病相关[J]. 中华内分泌代谢杂志, 2004, 20(6): 534-535.Xu JX, Xu BL, Yang MG, et al. -429T/C polymorphism of RAGE gene promoter is associated with type 2 diabetic nephropathy[J].Chin J Endocrinol Metab, 2004, 20(6): 534-535.
16.	Kang P, Tian C, Jia C. Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy[J]. Gene, 2012, 500(1): 1-9. DOI: 10.1016/j.gene.2012.03.056.
17.	Yuan D, Yuan D, Liu Q. Association of the receptor for advanced glycation end products gene polymorphisms with diabetic retinopathy in type 2 diabetes: a meta-analysis[J]. Ophthalmologica, 2012, 227(4): 223-232. DOI: 10.1159/000335628.
18.	Niu W, Qi Y, Wu Z, et al. A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus[J]. Mol Cell Endocrinol, 2012, 358(1): 9-17. DOI: 10.1016/j.mce.2012.02.010.
19.	顾喆瑶, 姚勇, 谢田华, 等. RAGE基因-429T＞C多态性与无锡汉族人群糖尿病视网膜病变的相关性[J]. 中华眼视光学与视觉科学杂志, 2015, 17(2):81-85. DOI:10.3760/cma.j.issn.1674-845X.2015.02.05.Gu ZY, Yao Y, Xie TH, et al. Correlation analysis of the -429T > C polymorphism of advanced glycation end products of the receptor gene and type 2 diabetic retinopathy in Han people in the Wuxi area[J]. Chin J Ophthalmol Vis Sci, 2015, 17(2):81-85. DOI:10.3760/cma.j.issn.1674-845X.2015.02.05.
20.	Bansal S, Chawla D, Banerjee BD, et al. Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients[J]. Gene, 2013, 526(2): 325-330. DOI: 10.1016/j.gene.2013.05.013.
21.	Yoshioka K, Yoshida T, Takakura Y, et al. Relation between polymorphisms G1704T and G82S of rage gene and diabetic retinopathy in Japanese type 2 diabetic patients[J]. Intern Med, 2005, 44(5): 417-421.
22.	Kankova K, Beranek M, Hajek D, et al. Polymorphisms 1704G/T, 2184A/G, and 2245G/A in the rage gene are not associated with diabetic retinopathy in NIDDM: pilot study[J]. Retina, 2002, 22(1): 119-121.

1. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications[J]. N Engl J Med, 1988, 318(20): 1315-1321. DOI: 10.1056/NEJM198805193182007.
2. Barile GR, Pachydaki SI, Tari SR, et al. The RAGE axis in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2005, 46(8): 2916-2924. DOI:10.1167/iovs.04-1409.
3. Yamagishi S, Maeda S, Matsui T, et al. Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes[J]. Biochim Biophys Acta, 2012, 1820(5): 663-671.DOI: 10.1016/j.bbagen.2011.03.014.
4. Ng ZX, Kuppusamy UR, Tajunisah I, et al. Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysian with type 2 diabetic retinopathy[J]. Diabetes Res Clin Pract, 2012, 95(3): 372-377. DOI: 10.1016/j.diabres.2011.11.005.
5. Ramprasad S, Radha V, Mathias RA, et al. Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India[J]. Eye (Lond), 2007, 21(3): 395-401. DOI:10.1038/sj.eye.6702239.
6. Tripathi AK, Chawla D, Bansal S, et al. Association of RAGE gene polymorphism with vascular complications in Indian type 2 diabetes mellitus patients[J]. Diabetes Res Clin Pract, 2014, 103(3): 474-481. DOI: 10.1016/j.diabres.2013.12.004.
7. Vanita V. Association of RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms with diabetic retinopathy in T2DM patients from north India[J]. Diabetes Res Clin Pract, 2014, 104(1): 155-162. DOI: 10.1016/j.diabres.2013.12.059.
8. 顾喆瑶, 姚勇, 谢田华, 等. 无锡地区汉族人群RAGE基因启动子区-374T/A多态性与糖尿病视网膜病变的相关研究[J]. 眼科新进展, 2014, 34(7): 655-657,661. DOI:10.13389/j.cnki.rao.2014.0179.Gu ZY, Yao Y, Xie TH, et al. Association analysis of advanced glycation end products gene receptor-374T/A poly-morphisms in Han people of Wuxi area with type 2 diabetic retinopathy[J]. Rec Adv Ophthalmol, 2014, 34(7): 655-657,661. DOI:10.13389/j.cnki.rao.2014.0179.
9. Zhang HM, Chen LL, Wang L, et al. Association of 1704G/T and G82S polymorphisms in the receptor for advanced glycation end products gene with diabetic retinopathy in Chinese population[J]. J Endocrinol Invest, 2009, 32(3): 258-262.
10. Yang L, Wu Q, Li Y, et al. Association of the receptor for advanced glycation end products gene polymorphisms and circulating RAGE levels with diabetic retinopathy in the Chinese population[J/OL]. J Diabetes Res, 2013, 2013: 264579[2013-11-04]. http://dx.doi.org/10.1155/2013/264579.
11. 李娜, 杨秀芬, 邓禹, 等. 2型糖尿病患者自我管理水平与糖尿病视网膜病变的相关性研究[J].中华眼科杂志, 2013, 49(6): 500-506. DOI: 10.3760/cma.j.issn.0412-4081.2013.06.007.Li N, Yang XF, Deng Y, et al. Diabetes self-management and its association with diabetic retinopathy in patients with type 2 diabetes[J]. Chin J Ophthalmol, 2013, 49(6): 500-506. DOI: 10.3760/cma.j.issn.0412-4081.2013.06.007.
12. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10[J]. Ophthalmology, 1991, 98 Suppl 5 : S786-806.
13. Yang X, Deng Y, Gu H, et al. 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.
14. Hudson BI, Stickland MH, Futers TS, et al. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy[J]. Diabetes, 2001, 50(6): 1505-1511. DOI: 10.2337/diabetes.50.6.1505.
15. 徐积兄, 徐碧林, 杨明功, 等. RAGE基因启动区-429T/C多态与2型糖尿病肾病相关[J]. 中华内分泌代谢杂志, 2004, 20(6): 534-535.Xu JX, Xu BL, Yang MG, et al. -429T/C polymorphism of RAGE gene promoter is associated with type 2 diabetic nephropathy[J].Chin J Endocrinol Metab, 2004, 20(6): 534-535.
16. Kang P, Tian C, Jia C. Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy[J]. Gene, 2012, 500(1): 1-9. DOI: 10.1016/j.gene.2012.03.056.
17. Yuan D, Yuan D, Liu Q. Association of the receptor for advanced glycation end products gene polymorphisms with diabetic retinopathy in type 2 diabetes: a meta-analysis[J]. Ophthalmologica, 2012, 227(4): 223-232. DOI: 10.1159/000335628.
18. Niu W, Qi Y, Wu Z, et al. A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus[J]. Mol Cell Endocrinol, 2012, 358(1): 9-17. DOI: 10.1016/j.mce.2012.02.010.
19. 顾喆瑶, 姚勇, 谢田华, 等. RAGE基因-429T＞C多态性与无锡汉族人群糖尿病视网膜病变的相关性[J]. 中华眼视光学与视觉科学杂志, 2015, 17(2):81-85. DOI:10.3760/cma.j.issn.1674-845X.2015.02.05.Gu ZY, Yao Y, Xie TH, et al. Correlation analysis of the -429T > C polymorphism of advanced glycation end products of the receptor gene and type 2 diabetic retinopathy in Han people in the Wuxi area[J]. Chin J Ophthalmol Vis Sci, 2015, 17(2):81-85. DOI:10.3760/cma.j.issn.1674-845X.2015.02.05.
20. Bansal S, Chawla D, Banerjee BD, et al. Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients[J]. Gene, 2013, 526(2): 325-330. DOI: 10.1016/j.gene.2013.05.013.
21. Yoshioka K, Yoshida T, Takakura Y, et al. Relation between polymorphisms G1704T and G82S of rage gene and diabetic retinopathy in Japanese type 2 diabetic patients[J]. Intern Med, 2005, 44(5): 417-421.
22. Kankova K, Beranek M, Hajek D, et al. Polymorphisms 1704G/T, 2184A/G, and 2245G/A in the rage gene are not associated with diabetic retinopathy in NIDDM: pilot study[J]. Retina, 2002, 22(1): 119-121.

Chinese Journal of Ocular Fundus Diseases

Association of -429T/C and G1704 polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy

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