Single nucleotide polymorphisms of vascular endothelial growth factor gene intron 2 are markers for early progression of diabetic retinopathy in Japanese with type 1 diabetes.
BACKGROUND
Few studies investigated the relationship between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) gene and time to the development and progression of diabetic retinopathy.


METHODS
Eight SNPs of VEGF gene were typed using TaqMan assays in 175 Japanese patients with type 1 diabetes. Fundi were evaluated longitudinally. The overall mean HbA1c value was calculated to assess long-term glycemic control.


RESULTS
Cumulative incidence of severe nonproliferative diabetic retinopathy (NPDR) differed among genotypes in rs833070 and rs2146323, both of which located in intron 2. Homozygotes for the minor alleles of rs833070, rs2146323, and rs699947, which were in strong linkage disequilibrium, showed earlier progression to severe NPDR than those with other genotypes (p = 0.010, p = 0.011, and p = 0.031, respectively). Cox proportional hazards analysis showed that homozygosity for the minor allele of rs833070 or rs2146323 was marginally insignificant as risk factor for severe NPDR, but significant after the mean HbA1c value was deleted from the model [hazard ratio (95% confidence interval): 1.67 (1.01-2.54), p = 0.047 and 1.67 (1.01-2.74), p = 0.047, respectively].


CONCLUSIONS
Certain SNPs in intron 2 of the VEGF gene are associated with early progression of retinopathy in Japanese patients with type 1 diabetes, though their contributions were weakened by glycemic exposure.
Nakanishi
Koji
K
Department of General Internal Medicine and Metabolism, Toranomon Hospital, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, Kanagawa 213-8587, Japan. koji01@toranomon.gr.jp
Watanabe
Chizuru
C
D000328:Adult; D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D005819:Genetic Markers; D006442:Glycated Hemoglobin; D042461:Vascular Endothelial Growth Factor A