Skip to main content

Advertisement

SpringerLink
Log in

Genetics of diabetic retinopathy

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Diabetes is rapidly increasing in frequency with an attendant toll of complications, including diabetic retinopathy. Although the underlying mechanisms remain elusive, genetic susceptibility is key to both types 1 and 2 diabetes and is increasingly recognized for its contribution to diabetic complications. In this article we review the evidence connecting genetic susceptibility to diabetic retinopathy. Elucidating the susceptibility genes and pathways should permit strategies to slow and reverse the troubling trends for the population, families, and individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Williams R, Airey M, Baxter H, et al.: Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye 2004, 18:963–983.

    Article  PubMed  CAS  Google Scholar 

  2. Leslie RD, Pyke DA: Diabetic retinopathy in identical twins. Diabetes 1982, 31:19–21.

    Article  PubMed  CAS  Google Scholar 

  3. Rema M, Saravanan G, Deepa R, Mohan V: Familial clustering of diabetic retinopathy in South Indian type 2 diabetic patients. Diabet Med 2002, 19:910–916.

    Article  PubMed  CAS  Google Scholar 

  4. Clustering of long-term complications in families with diabetes in the Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group [no authors listed]. Diabetes 1997, 46:1829–1839.

  5. Hallman DM, Huber JC, Gonzalez VH, et al.: Familial aggregation of severity of diabetic retinopathy in Mexican Americans from Starr County, Texas. Diabetes Care 2005, 28:1163–1168.

    Article  PubMed  Google Scholar 

  6. Klein R, Klein BEK: Diabetic eye disease. Lancet 1997, 350:197–204.

    Article  PubMed  CAS  Google Scholar 

  7. Warpeha KM, Chakravarthy U: Molecular genetics of microvascular disease in diabetic retinopathy. Eye 2003, 17:305–311.

    Article  PubMed  CAS  Google Scholar 

  8. Laleh L, Humphries SE: The genetics of stroke. Curr Opin Lipidol 2005, 16:193–199.

    Article  Google Scholar 

  9. Agarwal A, Williams GH, Fisher ND: Genetics of human hypertension. Trends Endocrinol Metab 2005, 16:127–133.

    Article  PubMed  CAS  Google Scholar 

  10. Petrovic MG, Peterlin B, Hawlina M, Petrovic D: Aldose reductase (AC)n gene polymorphism and susceptibility to diabetic retinopathy in type 2 diabetes in Caucasians. J Diabetes Complications 2005, 19:70–73.

    Article  PubMed  Google Scholar 

  11. Sivenius K, Niskanen L, Voutiloainen-Kaunisto R, et al.: Aldose reductase gene polymorphisms and susceptibility to microvascular complications in type 2 diabetes. Diabet Med 2004, 21:1325–1333.

    Article  PubMed  CAS  Google Scholar 

  12. Amano S, Yamagishi S, Koda Y, et al.: Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy. Med Hypotheses 2003, 60:550–551.

    Article  PubMed  CAS  Google Scholar 

  13. Frank RN: Diabetic retinopathy. N Engl J Med 2005, 350:48–58.

    Article  Google Scholar 

  14. Wheeler DL, Barrett T, Benson DA, et al.: Database resources of the National Center for Biotechnology Information. Nucleic Acids Research 2005, 33:D39-D45.

    Article  PubMed  CAS  Google Scholar 

  15. Altshuler D, Brooks LD, Chakravarti A, et al.: A haplotype map of the human genome. Nature 2005, 437:1299–1320.

    Article  CAS  Google Scholar 

  16. Maniatis N, Morton NE, Gibson J, et al.: The optimal measure of linkage disequilibrium reduces error in association mapping of affection status. Hum Mol Genet 2005, 14:145–153. The ability to access more and more of the extant genetic variation permits the development of strategies for systemically surveying the genome. A large part of this will be how to efficiently combine variation data as one moves across a gene, region, or genome to determine the impact of variation on risk. Haplotype tagging, disequilibrium considerations, and the like will play an important role and are discussed in this article.

    Article  PubMed  CAS  Google Scholar 

  17. de Bakker PIW, Yelensky R, Pe'er I, et al.: Efficiency and power in genetic association studies. Nat Genet 2005, 11:1217–1223.

    Article  CAS  Google Scholar 

  18. Roybal CN, Hunsaker LA, Barbash O, et al.: The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism. J Biol Chem 2005, 280:20331–20339.

    Article  PubMed  CAS  Google Scholar 

  19. Awata T, Kurihara S, Takata N, et al.: Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and macular retinal thickness in type 2 diabetes. Biochem Biophys Res Commun 2005, 333:679–685.

    Article  PubMed  CAS  Google Scholar 

  20. Klein RL, McHenry MB, Lok KH, et al.: Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes: associations with microvascular disease complications in the DCCT/EDIC cohort. J Diabetes Complications 2005, 19:18–25. This paper is illustrative of an approach where information on genetic variation of a trait is coupled with data regarding the gene product and a combined analysis employed to determine associations. In this manner, possible biological mechanisms are considered simultaneously with the genetic variation.

    Article  PubMed  Google Scholar 

  21. Donnelly R, Idris I, Forrester JV: Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research. Br J Ophthalmol 2004, 88:145–151.

    Article  PubMed  CAS  Google Scholar 

  22. The effect of ruboxistaurin on visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy. Initial results of the Protein Kinase C beta Inhibitor Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. PKC-DRS Study Group [no authors listed]. Diabetes 2005, 54:2188–2197.

  23. Ikeda Y, Suehiro T, Osaki F, et al.: Polymorphisms in the 5’-upstream region of the PKCbeta gene in Japanese patients with type 2 diabetes. Diabet Med 2004, 21:1113–1120.

    Article  PubMed  CAS  Google Scholar 

  24. Brownlee M: Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813–820.

    Article  PubMed  CAS  Google Scholar 

  25. Poulaki V, Joussen AM, Mitsiades N, et al.: Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy. AmJ Pathol 2004, 165:457–469.

    CAS  Google Scholar 

  26. Hamaoui K, Butt A, Powrie J, Swaminathan R: Real-time quantitative PCR measurement of circulatory rhodopsin mRNA in healthy subjects and patients with diabetic retinopathy. Ann N Y Acad Sci 2004, 1022:152–156.

    Article  PubMed  CAS  Google Scholar 

  27. Sassa Y, Hata Y, Aiello LP, et al.: Bifunctional properties of peroxisome proliferators-activated receptor gamma1 in KDR gene regulation mediated via interaction with both Sp1 and Sp3. Diabetes 2004, 53:1222–1229.

    Article  PubMed  CAS  Google Scholar 

  28. Mackness B, Durrington PN, Abuashia B, et al.: Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy. Clin Sci 2000, 98:355–363.

    Article  PubMed  CAS  Google Scholar 

  29. Zintzaras E, Chatzoulis DZ, Karabatsas CH, Stefanidis I: The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis. J Hum Genet 2005, 50:267–275. With the proliferation of candidate gene studies and the often ambiguous results, there must be strategies for combining data across multiple studies. Meta-analysis provides one such approach and is illustrated in this paper.

    Article  PubMed  CAS  Google Scholar 

  30. Davies JL, Kawaguchi Y, Bennett ST, et al.: A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994, 371:130–136.

    Article  PubMed  CAS  Google Scholar 

  31. Horikawa Y, Oda N, Cox NJ, et al.: Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000, 26:163–175.

    Article  PubMed  CAS  Google Scholar 

  32. Sawcer SJ, Maranian M, Singlehurst S, et al.: Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping. Hum Mol Genet 2004, 13:1943–1949.

    Article  PubMed  Google Scholar 

  33. Imperatore G, Hanson RL, Pettitt DJ, et al.: Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Diabetes 1998, 47:821–830.

    Article  PubMed  CAS  Google Scholar 

  34. Rodin AS, Boerwinkle E: Mining genetic epidemiology data with Bayesian networks I: Bayesian networks and example application (plasma apoE levels). Bioinformatics 2005, 21:3273–3278.

    Article  PubMed  CAS  Google Scholar 

  35. Moss AJ, Ryan D, Oakes D, et al.: Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction. Am J Cardiol 2005, 96:177–182.

    Article  PubMed  Google Scholar 

  36. Sadee W, Dai Z: Pharmacogenetics/genomics and personalized medicine. HuM Mol Genet 2005, 14(suppl 2): R207-R214.

    Article  PubMed  CAS  Google Scholar 

  37. Magrini A, Bottini N, Nicotra M, et al.: Smoking and the genetics of signal transduction: an association study on retinopathy in type 1 diabetes. Am J Med Sci 2002, 324:310–313.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Human Genetics Center, The University of Texas Health Science Center at Houston, PO Box 20186, 77225, Houston, TX, USA

    Craig L. Hanis PhD

Authors
  1. Craig L. Hanis PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Michael Hallman PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Craig L. Hanis PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hanis, C.L., Hallman, D.M. Genetics of diabetic retinopathy. Curr Diab Rep 6, 155–161 (2006). https://doi.org/10.1007/s11892-006-0027-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-006-0027-6

Keywords

Search

Navigation