A Common Polymorphism in the 5′-Untranslated Region of the VEGF Gene Is Associated With Diabetic Retinopathy in Type 2 Diabetes

A Common Polymorphism in the 5′-Untranslated Region of the VEGF Gene Is Associated With Diabetic Retinopathy in Type 2 Diabetes Takuya Awata , Kiyoaki Inoue , Susumu Kurihara , Tomoko Ohkubo , Masaki Watanabe , Kouichi Inukai , Ikuo Inoue and Shigehiro Katayama From the Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan Abstract Vascular endothelial growth factor (VEGF), a major mediator of vascular permeability and angiogenesis, may play a pivotal role in mediating the development and progression of diabetic retinopathy. In the present study, we examined the genetic variations of the VEGF gene to assess its possible relation to diabetic retinopathy in type 2 diabetic patients. Among seven common polymorphisms in the promoter region, 5′-untranslated region (UTR) and 3′UTR of the VEGF gene, genotype distribution of the C(−634)G polymorphism differed significantly ( P = 0.011) between patients with ( n = 150) and without ( n = 118) retinopathy, and the C allele was significantly increased in patients with retinopathy compared with those without retinopathy ( P = 0.0037). The odds ratio (OR) for the CC genotype of C(−634)G to the GG genotype was 3.20 (95% CI 1.45–7.05, P = 0.0046). The −634C allele was significantly increased in patients with nonproliferative diabetic retinopathy (non-PDR) ( P = 0.0026) and was insignificantly increased in patients with proliferative diabetic retinopathy (PDR) ( P = 0.081) compared with patients without retinopathy, although frequencies of the allele did not differ significantly between the non-PDR and PDR groups. Logistic regression analysis revealed that the C(−634)G polymorphism was strongly associated with an increased risk of retinopathy ( P = 0.0018). Furthermore, VEGF serum levels were significantly higher in healthy subjects with the CC genotype of the C(−634)G polymorphism than in those with the other genotypes. These data suggest that the C(−634)G polymorphism in the 5′UTR of the VEGF gene is a novel genetic risk factor for diabetic retinopathy. Footnotes Address correspondence and reprint requests to Dr. Takuya Awata, the Fourth Department of Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan. E-mail: awata{at}saitama-med.ac.jp . Received for publication 11 June 2001 and accepted in revised form 11 January 2002. LPS, lipopolysaccharide; non-PDR, nonproliferative diabetic retinopathy; OR, odds ratio; PBMC, peripheral blood mononuclear ce