title: A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes.
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.
authors.affiliation: Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan. awata@saitama-med.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Inoue
authors.forename: Susumu
authors.initials: S
authors.lastname: Kurihara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Masaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Inoue
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008222:Lymphokines / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D020121:5' Untranslated Regions; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors