eNOS gene polymorphism association with retinopathy in type 1 diabetes.
OBJECTIVE
Nitric oxide (NO) is a major mediator in vascular biology, regulating blood pressure and regional blood flow. NO and the enzymes required for its production may contribute to the aetiology of vascular pathologies. In diabetes, over-production of NO might play a role in the development of diabetic nephropathy, while reduced NO production may be related to the development of diabetic retinopathy and neuropathy, where VEGF (vascular endothelial growth factor) levels are increased in a counter regulatory manner. Among the three nitric oxide synthase (NOS) enzymes most attention has focussed on endothelial NOS (eNOS) because of its relevance to angiopathies.


METHODS
In this study the influence of a single nucleotide polymorphism at position -786 in the eNOS gene, where there is a C/T base substitution, on development of type 1 diabetes mellitus (T1DM) and its microvascular complications was studied in 249 British Caucasian type 1 diabetics using a case-control association design. Genotyping was carried out using PCR-RFLP technique.


RESULTS
There was a significant association between the polymorphism -786*C/T and both T1DM and diabetic retinopathy. The distribution of eNOS gene polymorphism genotype frequencies showed a significant difference observed between diabetic patients and healthy controls [CC+CT vs. TT p = 0.05, OR = 1.5 95%CI(0.9-2.5)]. The genotype frequencies for eNOS gene polymorphism was also significantly different between diabetic retinopaths and healthy controls [CC+CT vs. TT p = 0.0000 OR = 3.4 95%CI(1.9-6.1) No significant differences for eNOS allele and genotype frequencies were found in other groups compared to the controls.


CONCLUSIONS
Therefore, eNOS gene variation may be a factor in the genetic propensity to T1DM and diabetic retinopathy that may have a prognostic value or may suggest interventional approaches to regulate eNOS in patients with diabetes.
Bazzaz
Javad Tavakkoly
JT
Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran. tavakkolybazzazj@tums.ac.ir
Amoli
Mahsa M
MM
Pravica
Vera
V
Chandrasecaran
Ramesh
R
Boulton
Andrew J
AJ
Larijani
Bagher
B
Hutchinson
Ian V
IV
D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005838:Genotype; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom; D044465:White People
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III