RT Journal Article SR Electronic T1 Multiple Variants in Vascular Endothelial Growth Factor (VEGFA) Are Risk Factors for Time to Severe Retinopathy in Type 1 Diabetes JF Diabetes JO Diabetes FD American Diabetes Association SP 2161 OP 2168 DO 10.2337/db07-0376 VO 56 IS 8 A1 Al-Kateb, Hussam A1 Mirea, Lucia A1 Xie, Xinlei A1 Sun, Lei A1 Liu, Michelle A1 Chen, Hongtao A1 Bull, Shelley B. A1 Boright, Andrew P. A1 Paterson, Andrew D. YR 2007 UL http://diabetes.diabetesjournals.org/content/56/8/2161.abstract AB OBJECTIVE—We sought to determine if any common variants in the gene for vascular endothelial growth factor (VEGFA) are associated with long-term renal and retinal complications in type 1 diabetes.RESEARCH DESIGN AND METHODS—A total of 1,369 Caucasian subjects with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study had an average of 17 retinal photographs and 10 renal measures over 15 years. In the DCCT/EDIC, we studied 18 single nucleotide polymorphisms (SNPs) in VEGFA that represent all linkage disequilibrium bins (pairwise r2 ≥ 0.64) and tested them for association with time to development of severe retinopathy, three or more step progression of retinopathy, clinically significant macular edema, persistent microalbuminuria, and severe nephropathy.RESULTS—In a global multi-SNP test, there was a highly significant association of VEGFA SNPs with severe retinopathy (P = 6.8 × 10−5)—the four other outcomes were all nonsignificant. In survival analyses controlling for covariate risk factors, eight SNPs showed significant association with severe retinopathy (P < 0.05). The most significant single SNP association was rs3025021 (hazard ratio 1.37 [95% CI 1.13–1.66], P = 0.0017). Family-based analyses of severe retinopathy provide evidence of excess transmission of C at rs699947 (P = 0.029), T at rs3025021 (P = 0.013), and the C-T haplotype from both SNPs (P = 0.035). Multi-SNP regression analysis including 15 SNPs, and allowing for pairwise interactions, independently selected 6 significant SNPs (P < 0.05).CONCLUSIONS—These data demonstrate that multiple VEGFA variants are associated with the development of severe retinopathy in type 1 diabetes.