Common sequence variation in the VEGFC gene is associated with diabetic retinopathy and diabetic macular edema

<p><strong>Purpose:</strong> To investigate associations between single nucleotide polymorphisms (SNPs) in the <em>VEGFC</em> gene and the development of diabetic retinopathy (DR) in white patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM).</p> <p><strong>Design:</strong> Cross-sectional, case control study.</p> <p><strong>Participants:</strong> White patients with T1DM or T2DM (<i>n</i> = 2899) were recruited from ophthalmology and endocrine clinics in Australia and the United Kingdom. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be receiving oral hypoglycemic treatment or insulin.</p> <p><strong>Methods:</strong> Participants with DM but “no DR” (<i>n</i> = 980) were compared with 1919 participants with DM and “any DR.” Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (<i>P</i> = 0.001; OR, 0.67; confidence interval [CI], 0.52–0.85), rs17697515 (<i>P</i> = .001; OR, 0.62; CI, 0.47–0.81), and rs2333526 (<i>P</i> = 0.005; OR, 0.69; CI, 0.54–0.90). rs17697515 Was also specifically associated with DME in those with T2DM (<i>P</i> = 0.004; OR, 0.53; CI, 0.35–0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development.</p> <p><strong>Main Outcome Measures:</strong> Odds ratios (ORs) were determined for associations with DR of <em>VEGFC</em> tag SNPs, individually and within haplotypes. Logistic regression was used to adjust for clinical covariates, including DM type, age, sex, DM duration, hypertension, nephropathy, HbA1c, and smoking./p> </p><p><strong>Results:</strong> Participants with DM but "no DR" (<i>n</i> = 980) were compared with 1919 participants with DM and "any DR." Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (<i>P</i> = 0.001; OR, 0.67; confidence interval [CI], 0.52-0.85), rs17697515 (<i>P</i> = 0.001; OR, 0.62; CI, 0.47-0.81), and rs2333526 (<i>P</i> = 0.005; OR, 0.69; CI, 0.54-0.90). rs17697515 Was also specifically associated with DME in those with T2DM (<i>P</i> = 0.004; OR, 0.53; CI, 0.35-0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development.</p> <p><strong>Conclusions:</strong> Significant associations were found between <em>VEGFC</em> tag SNPs (individually and within haplotypes) and the presence of any DR or DME in white participants with T1DM and T2DM.</p>