Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes.
OBJECTIVE
We examined the endothelial nitric oxide (eNOS) gene polymorphisms to assess its possible association with diabetic retinopathy and macular edema.


METHODS
A total of 226 patients with type 2 diabetes and 186 healthy subjects were studied. Type 2 diabetic patients consisted of 110 patients without retinopathy, 46 patients with nonproliferative diabetic retinopathy, and 71 patients with proliferative diabetic retinopathy. Diabetic macular edema was present in 48 patients. Three polymorphisms of the eNOS gene were determined: T-786C in the promoter region, 27-bp repeat in intron 4, and Glu298Asp in exon 7.


RESULTS
Close linkage disequilibrium was observed between the T-786C polymorphism and the 27-bp repeat, as has been previously reported, but Glu298Asp was not in linkage disequilibrium with the other two polymorphisms. The eNOS gene polymorphisms were not significantly associated with the presence of retinopathy or with retinopathy severity or type 2 diabetes itself. However, by both association study and multiple logistic regression analysis, the T-786C and 27-bp repeat polymorphisms were significantly associated with a risk of developing macular edema with the -786C allele and the "a" allele increasing the risk.


CONCLUSIONS
The present study suggests that the eNOS gene is a novel genetic risk factor for diabetic macular edema. The eNOS gene polymorphisms may contribute to the development of macular edema by impairing basal eNOS expression and resulting in the breakdown of the blood-retina barrier.
Awata
Takuya
T
The Fourth Department of Medicine, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan. awata@saitama-med.ac.jp
Neda
Tamotsu
T
Iizuka
Hiroyuki
H
Kurihara
Susumu
S
Ohkubo
Tomoko
T
Takata
Nobuki
N
Osaki
Masataka
M
Watanabe
Masaki
M
Nakashima
Youhei
Y
Sawa
Takahiro
T
Inukai
Kouichi
K
Inoue
Ikuo
I
Shibuya
Masayuki
M
Mori
Keisuke
K
Yoneya
Shin
S
Katayama
Shigehiro
S
D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008268:Macular Degeneration / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors
D017931:DNA Primers; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III