Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes

Purpose Endothelin-1, and constitutive endothelial nitric oxide synthase, have been implicated in the pathogenesis of diabetic retinopathy. We therefore screened polymorphisms within the genes encoding these two vasoactive agents in a sample of individuals with 15 years of diabetes and no retinopathy (ETDRS level 10 or better) and those with severe retinopathy (ETDRS level 50 or worse).Methods PCR primers for highly polymorphic sites within the EDN1 and NOS3 genes were used to genotype individuals with type 1 or type 2 diabetes with severe or no retinopathy. Allele frequencies were compared between groups using chi-squared analysis and adjusting for multiple comparisons.Results No significant differences were observed in allele frequencies for these two markers between the patients who had retinopathy and the patients who did not.Conclusion Polymorphic variability in the EDN1 and NOS3 genes does not appear to have a major impact on determining susceptibility or resistance to diabetic retinopathy.

[1]  P. Corvol,et al.  Ontogeny of endothelins-1 and -3, their receptors, and endothelin converting enzyme-1 in the early human embryo. , 1998, The Journal of clinical investigation.

[2]  D. McMillan.  Hemorheological studies in the diabetes control & complications trial , 1993 .

[3]  Y. Ouchi,et al.  Elevated blood pressure and craniofaclal abnormalities in mice deficient in endothelin-1 , 1994, Nature.

[4]  A. Laties,et al.  Peptidergic innervation of the retinal vasculature and optic nerve head. , 1990, Investigative ophthalmology & visual science.

[5]  B. Brenner,et al.  Endothelium-dependent vascular responses. Mediators and mechanisms. , 1989, The Journal of clinical investigation.

[6]  X. Jeunemaître,et al.  Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene to essential hypertension. , 1995, Circulation.

[7]  M. Brown,et al.  Genetic Variability of the ET‐1 and the ETA Receptor Genes in Essential Hypertension , 1995, Journal of Cardiovascular Pharmacology.

[8]  Alan W. Stitt,et al.  Endothelin expression in ocular tissues of diabetic and insulin-treated rats. , 1997, Investigative ophthalmology & visual science.

[9]  A. Donker,et al.  Endothelial dysfunction and pathogenesis of diabetic angiopathy. , 1997, Cardiovascular research.

[10]  R. Hammer,et al.  Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene. , 1998, Development.

[11]  P. Taylor,et al.  Glaxo/MRS Young Investigator Prize. Endothelium-mediated vascular function in insulin-dependent diabetes mellitus. , 1995, Clinical science.

[12]  D TOUSSAINT,et al.  Retinal vascular patterns. IV. Diabetic retinopathy. , 1961, Archives of ophthalmology.

[13]  P. Guillausseau,et al.  Diabetes: from phenotypes to genotypes. , 1997, Diabetes & metabolism.

[14]  R. Cohen,et al.  Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. , 1990, The Journal of clinical investigation.

[15]  M. Lathrop,et al.  Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene. , 1994, Biochemical and biophysical research communications.

[16]  R. D. Rudic,et al.  Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. , 1998, The Journal of clinical investigation.

[17]  D. Pyke,et al.  Diabetic Retinopathy in Identical Twins , 1982, Diabetes.

[18]  R. Klein,et al.  Ten-year incidence of visual loss in a diabetic population. , 1994, Ophthalmology.

[19]  Alan W. Stitt,et al.  Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. , 1998, Diabetes.

[20]  H. Cann,et al.  A short tandem repeat polymorphism at the endothelin 1 (EDN1) locus. , 1993, Human molecular genetics.

[21]  M. Moskowitz,et al.  Hypertension in mice lacking the gene for endothelial nitric oxide synthase , 1995, Nature.

[22]  G. King,et al.  Vascular dysfunction in diabetes mellitus , 1997, The Lancet.