Update on genetics and diabetic retinopathy

Clinical Ophthalmology

Volumn 9, Issue , 2015, Pages 2175-2193

  Hampton, Blake M ^a   Schwartz, Stephen G ^a   Brantley, Milam A ^b   Flynn, Harry W ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Diabetic retinopathy; Genetics; Genome wide association study; Single nucleotide polymorphism

Indexed keywords

ADIPONECTIN; ADVANCED GLYCATION END PRODUCT RECEPTOR; ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; ANDROGEN RECEPTOR; COMPLEMENT FACTOR H; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ERYTHROPOIETIN; GAMMA INTERFERON; GLUTATHIONE TRANSFERASE M1; GLUTATHIONE TRANSFERASE T1; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 6; MANGANESE SUPEROXIDE DISMUTASE; MONOCYTE CHEMOTACTIC PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PLASMINOGEN ACTIVATOR INHIBITOR 1; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR 7 LIKE 2; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCOUPLING PROTEIN 1; UNCOUPLING PROTEIN 2; VASCULOTROPIN;

ADIPONECTIN GENE; ADVANCED GLYCATION END PRODUCT RECEPTOR GENE; AMINO ACID SUBSTITUTION; ANDROGEN RECEPTOR GENE; CHIMERIN 2 GENE; COMPLEMENT FACTOR B GENE; COMPLEMENT FACTOR H GENE; DIABETIC RETINOPATHY; ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE; ERYTHROPOIETIN GENE; GENE; GENE EXPRESSION; GENE FUNCTION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; GLUTATHIONE TRANSFERASE M1 GENE; GLUTATHIONE TRANSFERASE T1 GENE; HEMATOPOIETICALLY EXPRESSED HOMEOBOX GENE; HUMAN; INTERCELLULAR ADHESION MOLECULE 1 GENE; INTERFERON GAMMA GENE; INTERLEUKIN 10 GENE; INTERLEUKIN 6 GENE; MANGANESE SUPEROXIDE DISMUTASE GENE; MONOCYTE CHEMOATTRACTANT PROTEIN 1 GENE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA GENE; PLASMINOGEN ACTIVATOR INHIBITOR 1 GENE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SLC GENE; TOLL LIKE RECEPTOR 4 GENE; TRANSCRIPTION FACTOR 7 LIKE 2 GENE; TRANSFORMING GROWTH FACTOR BETA1 GENE; TUMOR NECROSIS FACTOR ALPHA GENE; UNCOUPLING PROTEIN 1 GENE; UNCOUPLING PROTEIN 2 GENE; VEGF GENE;

EID: 84948179809     PISSN: 11775467     EISSN: 11775483     Source Type: Journal    
DOI: 10.2147/OPTH.S94508     Document Type: Review

References (144)

1. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics Fact Sheet: General Information and National Estimates on Diabetes in the United States. Publication No 02-3892. Bethesda, MD: US Department of Health and Human Services, National Institute of Health; 2000.
2. Ruta LM, Magliano DJ, Lemesurier R, Taylor HR, Zimmet PZ, Shaw JE. Prevalence of diabetic retinopathy in type 2 diabetes in developing and developed countries. Diabet Med. 2013;30(4):387-398.
3. Liew G, Klein R, Wong TY. The role of genetics in susceptibility to diabetic retinopathy. Int Ophthalmol Clin. 2009;49(2):35-52.
4. Moss SE, Klein R, Klein BE. Ten-year incidence of visual loss in a diabetic population. Ophthalmology. 1994;101(6):1061-1070.
5. Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA. 2010;304(6):649-656.
6. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556-564.
7. Wong TY, Klein R, Islam FM, et al. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol. 2006;141(3):446-455.
8. Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol. 2012;57(4):347-370.
9. Looker HC, Nelson RG, Chew E, et al. Genome-wide linkage analyses to identify loci for diabetic retinopathy. Diabetes. 2007;56(4):1160-1166.
10. Hietala K, Forsblom C, Summanen P, Groop PH; FinnDiane Study Group. Heritability of proliferative diabetic retinopathy. Diabetes. 2008;57(8):2176-2180.
11. Arar NH, Freedman BI, Adler SG, et al. Heritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest Ophthalmol Vis Sci. 2008;49(9):3839-3845.
12. Schwartz SG, Brantley MA Jr, Flynn HW Jr. Genetics and diabetic retinopathy. Curr Diabetes Rev. 2013;9(1):86-92.
13. Uhlmann K, Kovacs P, Boettcher Y, Hammes HP, Paschke R. Genetics of diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2006;114(6): 275-294.
14. Petrash JM. All in the family: aldose reductase and closely related aldo-keto reductases. Cell Mol Life Sci. 2004;61(7-8):737-749.
15. Burg MB, Ferraris JD, Dmitrieva NI. Cellular response to hyperosmotic stresses. Physiol Rev. 2007;87(4):1441-1474.
16. Wang Y, Ng MC, Lee SC, et al. Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes. Diabetes Care. 2003;26(8): 2410-2415.
17. Fujisawa T, Ikegami H, Kawaguchi Y, et al. Length rather than a specific allele of dinucleotide repeat in the 5′ upstream region of the aldose reductase gene is associated with diabetic retinopathy. Diabet Med. 1999;16(12):1044-1047.
18. Ichikawa F, Yamada K, Ishiyama-Shigemoto S, Yuan X, Nonaka K. Association of an (A-C)n dinucleotide repeat polymorphic marker at the 5′-region of the aldose reductase gene with retinopathy but not with nephropathy or neuropathy in Japanese patients with type 2 diabetes mellitus. Diabet Med. 1999;16(9):744-748.
19. Ikegishi Y, Tawata M, Aida K, Onaya T. Z-4 allele upstream of the aldose reductase gene is associated with proliferative retinopathy in Japanese patients with NIDDM, and elevated luciferase gene transcription in vitro. Life Sci. 1999;65(20):2061-2070.
20. Kumaramanickavel G, Sripriya S, Ramprasad VL, Upadyay NK, Paul PG, Sharma T. Z-2 aldose reductase allele and diabetic retinopathy in India. Ophthalmic Genet. 2003;24(1):41-48.
21. Uthra S, Raman R, Mukesh BN, et al. Diabetic retinopathy: validation study of ALR2, RAGE, iNOS and TNFB gene variants in a south Indian cohort. Ophthalmic Genet. 2010;31(4):244-251.
22. Olmos P, Futers S, Acosta AM, et al. (AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics. Diabetes Res Clin Pract. 2000;47(3):169-176.
23. Richeti F, Noronha RM, Waetge RT, et al. Evaluation of AC(n) and C(-106)T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy. Mol Vis. 2007;13:740-745.
24. Li Q, Xie P, Huang J, Gu Y, Zeng W, Song H. Polymorphisms and functions of the aldose reductase gene 5′ regulatory region in Chinese patients with type 2 diabetes mellitus. Chin Med J (Engl). 2002;115(2):209-213.
25. Park HK, Ahn CW, Lee GT, et al. (AC)(n) polymorphism of aldose reductase gene and diabetic microvascular complications in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2002;55(2):151-157.
26. Santos KG, Tschiedel B, Schneider J, Souto K, Roisenberg I. Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: relationship with polymorphisms in the aldose reductase, the plasminogen activator inhibitor-1 and the methylenetetrahydrofolate reductase genes. Diabetes Res Clin Pract. 2003;61(2):133-136.
27. Rezaee MR, Amiri AA, Hashemi-Soteh MB, et al. Aldose reductase C-106T gene polymorphism in type 2 diabetics with microangiopathy in Iranian individuals. Indian J Endocrinol Metab. 2015;19(1):95-99.
28. Deng Y, Yang XF, Gu H, et al. Association of C(-106)T polymorphism in aldose reductase gene with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus. Chin Med Sci J. 2014;29(1):1-6.
29. Zhou M, Zhang P, Xu X, Sun X. The relationship between aldose reductase C106T polymorphism and diabetic retinopathy: an updated meta-analysis. Invest Ophthalmol Vis Sci. 2015;56(4):2279-2289.
30. Ozüyaman B, Gödecke A, Küsters S, Kirchhoff E, Scharf RE, Schrader J. Endothelial nitric oxide synthase plays a minor role in inhibition of arterial thrombus formation. Thromb Haemost. 2005;93(6):1161-1167.
31. Zhao S, Li T, Zheng B, Zheng Z. Nitric oxide synthase 3 (NOS3) 4b/a, T-786C and G894T polymorphisms in association with diabetic retinopathy susceptibility: a meta-analysis. Ophthalmic Genet. 2012;33(4):200-207.
32. Cheema BS, Kohli HS, Sharma R, Bhansali A, Khullar M. Endothelial nitric oxide synthase gene polymorphism and type 2 diabetic retinopathy among Asian Indians. Acta Diabetol. 2012;49(6):481-488.
33. 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.
34. Cilenšek I, Mankoč S, Globočnik Petrovič M, Petrovič D. 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.
35. Santos KG, Crispim D, Canani LH, Ferrugem PT, Gross JL, Roisenberg I. 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.
36. Narne P, Ponnaluri KC, Siraj M, Ishaq M. Association analysis of polymorphisms in genes related to oxidative stress in South Indian type 2 diabetic patients with retinopathy. Ophthalmic Genet. 2015:1-8.
37. Ma ZJ, Chen R, Ren HZ, Guo X, Guo J, Chen LM. Association between eNOS 4b/a polymorphism and the risk of diabetic retinopathy in type 2 diabetes mellitus: a meta-analysis. J Diabetes Res. 2014;2014: 549747.
38. Kanková K, Márová I, Záhejský J, et al. Polymorphisms 1704G/T and 2184A/G in the RAGE gene are associated with antioxidant status. Metab Clin Exp. 2001;50(10):1152-1160.
39. Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Chua KH. Association analysis of -429T/C and -374T/A polymorphisms of receptor of advanced glycation end products (RAGE) gene in Malaysians with type 2 diabetic retinopathy. Diabetes Res Clin Pract. 2012;95(3):372-377.
40. 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. Ophthalmologica. 2012;227(4):223-232.
41. Vanita V. Association of RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms with diabetic retinopathy in T2DM patients from north India. Diabetes Res Clin Pract. 2014;104(1):155-162.
42. Ng ZX, Kuppusamy UR, Poh R, et al. Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients. Genet Mol Res. 2012;11(1):455-461.
43. 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.
44. 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. Mol Vis. 2012;18:2749-2757.
45. Gong JY, Sun YH. Association of VEGF gene polymorphisms with diabetic retinopathy: a meta-analysis. PLoS One. 2013;8(12):e84069.
46. Han L, Zhang L, Xing W, et al. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies. J Diabetes Res. 2014;2014:805801.
47. Yuan Y, Wen Z, Guan Y, et al. The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects. J Diabetes Complications. 2014;28(6):785-790.
48. Yang X, Deng Y, Gu H, et al. Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes. Mol Vis. 2014;20:200-214.
49. Lu Y, Ge Y, Shi Y, Yin J, Huang Z. Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic retinopathy: an updated meta-analysis. BMC Ophthalmol. 2013;13:56.
50. Wang H, Cheng JW, Zhu LS, et al. Meta-analysis of association between the -2578C/A polymorphism of the vascular endothelial growth factor and retinopathy in type 2 diabetes in Asians and Caucasians. Ophthalmic Res. 2014;52(1):1-8.
51. Shahin RM, Abdelhakim MA, Owid ME, El-Nady M. A study of VEGF gene polymorphism in Egyptian patients with diabetic retinopathy. Ophthalmic Genet. 2015:1-6.
52. Fan X, Wu Q, Li Y, et al. Association of polymorphisms in the vascular endothelial growth factor gene and its serum levels with diabetic retinopathy in Chinese patients with type 2 diabetes: a cross-sectional study. Chin Med J. 2014;127(4):651-657.
53. Choudhuri S, Chowdhury IH, Das S, et al. Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy. Mol Cell Biochem. 2015;405(1-2):265-279.
54. Qiu M, Xiong W, Liao H, Li F. VEGF -634G.C polymorphism and diabetic retinopathy risk: a meta-analysis. Gene. 2013;518(2): 310-315.
55. Bonnefond A, Saulnier PJ, Stathopoulou MG, et al. What is the contribution of two genetic variants regulating VEGF levels to type 2 diabetes risk and to microvascular complications? PLoS One. 2013;8(2):e55921.
56. Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8(11):1288-1295.
57. Sikka R, Raina P, Matharoo K, et al. TNF-α (g.-308G.A) and ADIPOQ (g.+45T.G) gene polymorphisms in type 2 diabetes and microvascular complications in the region of Punjab (North-West India). Curr Eye Res. 2014;39(10):1042-1051.
58. Li Y, Wu QH, Jiao ML, et al. Gene-environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy. J Diabetes Investig. 2015;6(1):56-66.
59. Nichols EM, Barbour TD, Pappworth IY, et al. An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy. Kidney Int. Epub July 29, 2015.
60. Imamura H, Konomoto T, Tanaka E, et al. Familial C3 glomerulonephritis associated with mutations in the gene for complement factor B. Nephrol Dial Transplant. 2015;30(5):862-864.
61. Wang J, Yang MM, Li YB, Liu GD, Teng Y, Liu XM. Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic patients. Mediators Inflamm. 2013;2013:748435.
62. Toni M, Hermida J, Toledo E, Goñi MJ, Díez Goñi N. Role of CFH and ARMS2 polymorphisms in retinopathy and coronary artery disease in type 1 diabetes. An Sist Sanit Navar. 2012;35(3):425-432. Sloverian.
63. Yuan S, Miller DW, Barnett GH, Hahn JF, Williams BR. Identification and characterization of human beta 2-chimaerin: association with malignant transformation in astrocytoma. Cancer Res. 1995;55(15):3456-3461.
64. Chen M, Lin WR, Lu CH, et al. Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients. J Diabetes Complications. 2014;28(4):460-463.
65. Hosseini SM, Boright AP, Sun L, et al. The association of previously reported polymorphisms for microvascular complications in a meta-analysis of diabetic retinopathy. Hum Genet. 2015;134(2):247-257.
66. De Lucas Cerrillo AM, Bond WS, Rex TS. Safety and angiogenic effects of systemic gene delivery of a modified erythropoietin. Gene Ther. 2015;22(5):365-373.
67. Song Q, Zhang Y, Wu Y, Zhou F, Qu Y. Association of erythropoietin gene polymorphisms with retinopathy in a Chinese cohort with type 2 diabetes mellitus. Clin Experiment Ophthalmol. 2015;43(6):544-549.
68. Doney AS, Lee S, Leese GP, Morris AD, Palmer CN. Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study. Circulation. 2005;111(22):2927-2934.
69. Cilenšek I, Mankoč S, Petrovič MG, Petrovič D. GSTT1 null genotype is a risk factor for diabetic retinopathy in Caucasians with type 2 diabetes, whereas GSTM1 null genotype might confer protection against retinopathy. Dis Markers. 2012;32(2):93-99.
70. Dadbinpour A, Sheikhha MH, Darbouy M, Afkhami-Ardekani M. Investigating GSTT1 and GSTM1 null genotype as the risk factor of diabetes type 2 retinopathy. J Diabetes Metab Disord. 2013;12(1):48.
71. Sun L, Zhang Y, Xiong Y. GSTM1 and GSTT1 null genotype and diabetic retinopathy: a meta-analysis. Int J Clin Exp Med. 2015;8(2):1677-1683.
72. Moasser E, Azarpira N, Shirazi B, Saadat M, Geramizadeh B. Genetic polymorphisms of glutathione-s-transferase M1 and T1 genes with risk of diabetic retinopathy in Iranian population. Iran J Basic Med Sci. 2014;17(5):351-356.
73. Rothlein R, Dustin ML, Marlin SD, Springer TA. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986;137(4):1270-1274.
74. Vinita K, Sripriya S, Prathiba K, et al. ICAM-1 K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case-control study. BMJ Open. 2012;2(4).
75. Fan WY, Liu NP. Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes. Int J Ophthalmol. 2015;8(3):603-607.
76. Su X, Chen X, Liu L, Chang X, Yu X, Sun K. Intracellular adhesion molecule-1 K469E gene polymorphism and risk of diabetic microvascular complications: a meta-analysis. PLoS One. 2013;8(7):e69940.
77. Sun H, Cong X, Sun R, Wang C, Wang X, Liu Y. Association between the ICAM-1 K469E polymorphism and diabetic retinopathy in type 2 diabetes mellitus: a meta-analysis. Diabetes Res Clin Pract. 2014;104(2):e46-e49.
78. Held TK, Weihua X, Yuan L, Kalvakolanu DV, Cross AS. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms, at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and interleukin-1. Infect Immun. 1999;67(1):206-212.
79. Rodrigues KF, Pietrani NT, Sandrim VC, et al. Association of a large panel of cytokine gene polymorphisms with complications and comorbidities in type 2 diabetes patients. J Diabetes Res. 2015;2015:605965.
80. Paine SK, Sen A, Choudhuri S, et al. Association of tumor necrosis factor α, interleukin 6, and interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects. Retina. 2012;32(6):1197-1203.
81. Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009;29(6):313-326.
82. Jeon HJ, Choi HJ, Park BH, Lee YH, Oh T. Association of monocyte chemoattractant protein-1 (MCP-1) 2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes. Yonsei Med J. 2013;54(3):621-625.
83. Kudlacek S, Schieder K, Kölbl H, et al. Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer. Gynecol Oncol. 1989;35(3):323-329.
84. Ninomiya H, Katakami N, Osonoi T, et al. Association between new onset diabetic retinopathy and monocyte chemoattractant protein-1 (MCP-1) polymorphism in Japanese type 2 diabetes. Diabetes Res Clin Pract. 2015;108(3):e35-e7.
85. Jiang Z, Hennein L, Xu Y, Bao N, Coh P, Tao L. Elevated serum monocyte chemoattractant protein-1 levels and its genetic polymorphism is associated with diabetic retinopathy in Chinese patients with type 2 diabetes. Diabet Med. Epub May 16, 2015.
86. Valenti L, Conte D, Piperno A, et al. The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. J Med Genet. 2004;41(12):946-950.
87. Haghighi SF, Salehi Z, Sabouri MR, Abbasi N. Polymorphic variant of MnSOD A16V and risk of diabetic retinopathy. Mol Biol (Mosk). 2015;49(1):114-118. Russian.
88. Sartori MT, Danesin C, Saggiorato G, et al. The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with inherited thrombophilia. Clin Appl Thromb Hemost. 2003;9(4):299-307.
89. Grant MB, Spoerri PE, Player DW, et al. Plasminogen activator inhibitor (PAI)-1 overexpression in retinal microvessels of PAI-1 transgenic mice. Invest Ophthalmol Vis Sci. 2000;41(8):2296-2302.
90. Zhang T, Pang C, Li N, Zhou E, Zhao K. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis. BMC Med. 2013;11:1.
91. Xu K, Liu X, Yang F, et al. PAI-1-675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study. PLoS One. 2013;8(11):e79150.
92. Zhuang H, Zhang X, Zhu C, et al. Molecular mechanisms of PPAR-γ governing MSC osteogenic and adipogenic differentiation. Curr Stem Cell Res Ther. Epub May 31, 2015.
93. Kwon KA, Yun J, Oh SY, et al. Clinical significance of peroxisome proliferator-activated receptor γ and TRAP220 in patients with operable colorectal cancer. Cancer Res Treat. Epub June 23, 2015.
94. Ma J, Li Y, Zhou F, Xu X, Guo G, Qu Y. Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians. Mol Vis. 2012;18:2352-2360.
95. Tariq K, Malik SB, Ali SH, et al. Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy. Mol Vis. 2013;19:710-717.
96. Fagerholm E, Ahlqvist E, Forsblom C, et al. SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes. Diabetologia. 2012;55(9):2386-2393.
97. Zhang Y, Meng N, Lv Z, Li H, Qu Y. The gene polymorphisms of UCP1 but not PPARγ and TCF7L2 are associated with diabetic retinopathy in Chinese type 2 diabetes mellitus cases. Acta Ophthalmol. 2015;93(3):e223-e229.
98. Kirchhoff K, Machicao F, Haupt A, et al. Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia. 2008;51(4):597-601.
99. Ciccacci C, Di Fusco D, Cacciotti L, et al. TCF7L2 gene polymorphisms and type 2 diabetes: association with diabetic retinopathy and cardiovascular autonomic neuropathy. Acta Diabetol. 2013;50(5):789-799.
100. Luo J, Zhao L, Chen AY, et al. TCF7L2 variation and proliferative diabetic retinopathy. Diabetes. 2013;62(7):2613-2617.
101. Fu LL, Lin Y, Yang ZL, Yin YB. Association analysis of genetic polymorphisms of TCF7L2, CDKAL1, SLC30A8, HHEX genes and microvascular complications of type 2 diabetes mellitus. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012;29(2):194-199. Chinese.
102. Sudchada P, Scarpace K. Transcription factor 7-like 2 polymorphisms and diabetic retinopathy: a systematic review. Genet Mol Res. 2014;13(3):5865-5872.
103. Hoerster R, Muether PS, Vierkotten S, Hermann MM, Kirchhof B, Fauser S. Upregulation of TGF-β1 in experimental proliferative vitreoretinopathy is accompanied by epithelial to mesenchymal transition. Graefes Arch Clin Exp Ophthalmol. 2014;252(1):11-16.
104. Huang SS, Huang JS. TGF-beta control of cell proliferation. J Cell Biochem. 2005;96(3):447-462.
105. Liu L, Jiao J, Wang Y, et al. TGF-beta1 gene polymorphism in association with diabetic retinopathy susceptibility: a systematic review and meta-analysis. PLoS One. 2014;9(4):e94160.
106. Bazzaz JT, Amoli MM, Taheri Z, Larijani B, Pravica V, Hutchinson IV. TGF-β1 and IGF-I gene variations in type 1 diabetes microangiopathic complications. J Diabetes Metab Disord. 2014;13(1):45.
107. Zareparsi S, Buraczynska M, Branham KE, et al. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. Hum Mol Genet. 2005;14(11):1449-1455.
108. Kohno H, Chen Y, Kevany BM, et al. Photoreceptor proteins initiate microglial activation via Toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal. J Biol Chem. 2013;288(21):15326-15341.
109. Singh K, Kant S, Singh VK, Agrawal NK, Gupta SK, Singh K. Toll-like receptor 4 polymorphisms and their haplotypes modulate the risk of developing diabetic retinopathy in type 2 diabetes patients. Mol Vis. 2014;20:704-713.
110. Xu Y, Jiang Z, Huang J, Meng Q, Coh P, Tao L. The association between toll-like receptor 4 polymorphisms and diabetic retinopathy in Chinese patients with type 2 diabetes. Br J Ophthalmol. 2015;99(9):1301-1305.
111. Fong LY, Ng CT, Zakaria ZA, et al. Asiaticoside inhibits TNF-α-induced endothelial hyperpermeability of human aortic endothelial cells. Phytother Res. Epub July 14, 2015.
112. Sesti LF, Crispim D, Canani LH, et al. The -308G.a polymorphism of the TNF gene is associated with proliferative diabetic retinopathy in Caucasian Brazilians with type 2 diabetes. Invest Ophthalmol Vis Sci. 2015;56(2):1184-1190.
113. Meng N, Zhang Y, Li H, Ma J, Qu Y. Association of tumor necrosis factor alpha promoter polymorphism (TNF-α 238 G/A and TNF-α 308 G/A) with diabetic mellitus, diabetic retinopathy and diabetic nephropathy: a meta-analysis. Curr Eye Res. 2014;39(2):194-203.
114. Nam M, Cooper MP. Role of energy metabolism in the Brown Fat Gene Program. Front Endocrinol (Lausanne). 2015;6:104.
115. Brondani LA, De Souza BM, Duarte GC, et al. The UCP1 -3826A/G polymorphism is associated with diabetic retinopathy and increased UCP1 and MnSOD2 gene expression in human retina. Invest Ophthalmol Vis Sci. 2012;53(12):7449-7457.
116. Shen Y, Wen Z, Wang N, et al. Investigation of variants in UCP2 in Chinese type 2 diabetes and diabetic retinopathy. PLoS One. 2014;9(11):e112670.
117. Kershaw RM, Siddiqui YH, Roberts D, Jayaraman PS, Gaston K. PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin. Oncogene. 2014;33(49):5592-5600.
118. Schweigel-Röntgen M. The families of zinc (SLC30 and SLC39) and copper (SLC31) transporters. Curr Top Membr. 2014;73:321-355.
119. Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Chua KH. Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy. J Diabetes Complications. 2012;26(5):388-392.
120. Chen P, Ong RT, Tay WT, et al. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry. PLoS One. 2013;8(11):e79767.
121. Wu L, Fernandez-Loaiza P, Sauma J, Hernandez-Bogantes E, Masis M. Classification of diabetic retinopathy and diabetic macular edema. World J Diabetes. 2013;4(6):290-294.
122. Klein R, Klein BE, Moss SE. The relationship of systemic hypertension to changes in the retinal vasculature: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc. 1997;95:329-348.
123. Cugati S, Cikamatana L, Wang JJ, Kifley A, Liew G, Mitchell P. Five-year incidence and progression of vascular retinopathy in persons without diabetes: the Blue Mountains Eye Study. Eye. 2006;20(11):1239-1245.
124. Lipner EM, Tomer Y, Noble JA, et al. HLA class I and II alleles are associated with microvascular complications of type 1 diabetes. Hum Immunol. 2013;74(5):538-544.
125. Lin HJ, Huang YC, Lin JM, Wu JY, Chen LA, Tsai FJ. Association of genes on chromosome 6, GRIK2, TMEM217 and TMEM63B (linked to MRPL14) with diabetic retinopathy. Ophthalmologica. 2013;229(1):54-60.
126. Sheu WH, Kuo JZ, Lee IT, et al. Genome-wide association study in a Chinese population with diabetic retinopathy. Hum Mol Genet. 2013;22(15):3165-3173.
127. Wang J, Yang MM, Rong SS, Ng TK, Li YB, Liu XM. Association of paraoxonase gene polymorphisms with diabetic nephropathy and retinopathy. Mol Med Rep. 2013;8(6):1845-1851.
128. Mankoč Ramuš S, Kumše T, Globočnik Petrovič M, Petrovič D, Cilenšek I. SNP rs2073618 of the osteoprotegerin gene is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes. Biomed Res Int. 2013;2013:364073.
129. Mcauley AK, Wang JJ, Dirani M, Connell PP, Lamoureux E, Hewitt AW. Replication of genetic loci implicated in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014;55(3):1666-1671.
130. Awata T, Yamashita H, Kurihara S, et al. A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA. PLoS One. 2014;9(11):e111715.
131. Zhong X, Du Y, Lei Y, Liu N, Guo Y, Pan T. Effects of vitamin D receptor gene polymorphism and clinical characteristics on risk of diabetic retinopathy in Han Chinese type 2 diabetes patients. Gene. 2015;566(2):212-216.
132. Upadhyay R, Robay A, Fakhro K, et al. Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population. J Transl Med. 2015;13:61.
133. Petrovic MG, Kruzliak P, Petrovic D. The rs6060566 of the reactive oxygen species modulator 1 (Romo-1) gene affects Romo-1 expression and the development of diabetic retinopathy in Caucasians with type 2 diabetes. Acta Ophthalmol. Epub March 30, 2015.
134. Li Z, Ni CL, Niu WY, Chang BC, Chen LM. The intestinal fatty acid binding protein-2 Ala54Thr polymorphism is associated with diabetic retinopathy in Chinese population. Diabetol Metab Syndr. 2015;7:23.
135. Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy. J Res Med Sci. 2014;19(11):1090-1098.
136. Mcauley AK, Dirani M, Wang JJ, Connell PP, Lamoureux EL, Hewitt AW. A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy. Diab Vasc Dis Res. 2015;12(2):133-138.
137. Liu NJ, Wu HH, Li YL, et al. An analysis of the association between a polymorphism of KCNJ11 and diabetic retinopathy in a Chinese Han population. Eur J Med Res. 2015;20:3.
138. Gong JY, Deng DT, Sun YH. Association of platelet glycoprotein receptor alpha2beta1 integrin and glycoprotein IIIa gene polymorphisms with diabetic retinopathy: evidence from 3007 subjects. Curr Eye Res. 2015;40(5):476-483.
139. Arndt C, Leclercq I, Nazeyrollas P, et al. Association of endothelial lipase Thr111Ile polymorphism with proliferative retinopathy in type 2 diabetes patients. Diabetes Metab. 2014;40(6):452-458.
140. Kajiwara A, Saruwatari J, Kita A, et al. Sex differences in the effect of cytochrome P450 2C19 polymorphisms on the risk of diabetic retinopathy: a retrospective longitudinal study in Japanese patients with type 2 diabetes. Pharmacogenet Genomics. 2013;23(12):717-720.
141. Buraczynska M, Wacinski P, Zukowski P, Dragan M, Ksiazek A. Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes. J Diabetes Complications. 2014;28(1):35-39.
142. Morita K, Saruwatari J, Miyagawa H, et al. Association between aldehyde dehydrogenase 2 polymorphisms and the incidence of diabetic retinopathy among Japanese subjects with type 2 diabetes mellitus. Cardiovasc Diabetol. 2013;12:132.
143. Yigit S, Karakus N, Inanir A. Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy. Mol Vis. 2013;19:1626-1630.
144. Ferreira FN, Crispim D, Canani LH, Gross JL, Dos Santos KG. Association study of sorbitol dehydrogenase -888G.C polymorphism with type 2 diabetic retinopathy in Caucasian-Brazilians. Exp Eye Res. 2013;115:140-143.