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Georgia Kaidonis, Kathryn P Burdon, Mark C Gillies, Rohan W Essex, John H Chang, Bishwanath Pal, Mark Daniell, Nikolai Petrovsky, Alex W Hewitt, Jamie E Craig; Common sequence variation in the VEGF-C gene is associated with diabetic retinopathy and diabetic macular edema in Caucasian diabetic patients.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1462.
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© ARVO (1962-2015); The Authors (2016-present)
The interaction between Vascular Endothelial Growth Factor C (VEGF-C), VEFG-A and their common receptor, VEGFR-2, has been shown to play a functional role in the pathogenesis of diabetic retinopathy (DR). The aim of this study was to investigate associations between single nucleotide polymorphisms (SNPs) in the VEGF-C gene and the development of DR in Caucasian patients with either type 1 (T1DM) or type 2 (T2DM) diabetes mellitus.
2907 Caucasian patients with T1DM or T2DM were recruited from ophthalmology and endocrine clinics in Australia and the United Kingdom. T2DM patients were required to have DM for a duration of at least 5 years, and be on oral hypoglycemic treatment or insulin. Participants were categorized according to their worst ever DR grading, as having ‘No DR’ (no history of non-proliferative DR (NPDR), proliferative DR (PDR) or diabetic macular edema (DME)), or ‘Any DR’ (further subclassified as NPDR, PDR, and/or DME). Clinical characteristics, diabetic control (HbA1c), and the presence of diabetic complications were determined at the time of recruitment. Genotyping was successfully performed for 12 VEGF-C tag SNPs. Odds ratios (OR) were determined for associations of VEGF-C tag SNPs, individually and within haplotypes, with diabetic retinopathy. Logistic regression allowed for adjustment of clinical covariates including DM type, age, sex, duration of DM, hypertension, nephropathy and HbA1c.
1022 diabetic participants with No DR were compared with 1885 diabetic participants with Any DR. Three VEGF-C SNPs were associated with DR following logistic regression, and after correction for multiple SNP testing: rs17697419 (p=0.001; OR, 0.68; CI, 0.54-0.86), rs17697515 (p=0.001; OR, 0.65; CI, 0.50-0.84) and rs1485766 (p=0.005; OR, 1.22; CI, 1.06-1.40). rs17697515 was also specifically associated with DME (p=0.002; OR, 0.68; CI, 0.53-0.86). Haplotype analysis revealed 3 significant haplotypes, including 1 risk, and 2 protective haplotypes for DR development.
This study is the first to evaluate sequence variation with the VEGF-C gene in diabetic patients with and without DR. Significant associations were found between VEGF-C tag SNPs (individually, and within haplotypes) and the presence of any DR, and DME, in a large cohort of Caucasian participants with both T1DM and T2DM.
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