Genetic variants in vegf receptor genes are associated with diabetic retinopathy

Purpose: Few studies have explored genetic variants in vascular endothelial growth factor receptor (VEGFR) genes and association with diabetic retinopathy (DR). We tested the association of single nucleotide polymorphisms (SNPs) in VEGFR genes with DR. Method: SNPs in VEGFR1, VEGFR2 and VEGFR3 genes were imputed into our cohort of 1598 diabetics previously genotyped on the OmniExpress array by comparison to the European reference population in the 1000 Genomes Project. Binary logistic regression for multivariate analysis (adjusting for age, sex, duration of diabetes, HbA1c and hypertension) was performed to identify associations with blinding DR (proliferative DR or clinically significant macula oedema) compared with diabetic controls (no DR) in type 1 and type 2 diabetes. Top ranking SNPs and SNPs with predicted functional changes from the literature were genotyped in a larger sample (n = 3694) to confirm their association with DR. Results: 2031 SNPs were successfully imputed. Three SNPs with P < 0.001 or with P < 0.05 in both types of diabetes, and 11 SNPs previously reported in the literature were genotyped in the larger sample. Two SNPs in VEGFR1 survived Bonferroni correction (P < 0.0036 for 14 SNPs tested) in their association with blinding DR in type 2 diabetes: rs56138102 (OR 3.97, P = 0.00061) and rs7990486 (OR 3.21, P = 0.0012). No significant associations were found for other DR phenotypes or in type 1 diabetes. Conclusion: Genetic variants in VEGFR1 are significantly associated with blinding DR in type 2 diabetes, in a large Caucasian Australian sample.