PMID- 26072347 OWN - NLM STAT- MEDLINE DCOM- 20151116 LR - 20221207 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 122 IP - 9 DP - 2015 Sep TI - Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema. PG - 1828-36 LID - S0161-6420(15)00429-7 [pii] LID - 10.1016/j.ophtha.2015.05.004 [doi] AB - PURPOSE: To investigate associations between single nucleotide polymorphisms (SNPs) in the VEGFC gene and the development of diabetic retinopathy (DR) in white patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional, case control study. PARTICIPANTS: White patients with T1DM or T2DM (n = 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. METHODS: Participants were categorized according to their worst-ever DR grading, as having "no DR" (no history of nonproliferative DR [NPDR], proliferative DR [PDR], or diabetic macular edema [DME]) or "any DR" (further subclassified as NPDR or PDR, without or with DME). Clinical characteristics, glycemic control (hemoglobin A1c [HbA1c]), and presence of diabetic complications were determined at recruitment. Genotyping was performed for 13 VEGFC tag SNPs. MAIN OUTCOME MEASURES: Odds ratios (ORs) were determined for associations with DR of VEGFC 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. RESULTS: Participants with DM but "no DR" (n = 980) were compared with 1919 participants with DM and "any DR." Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (P = 0.001; OR, 0.67; confidence interval [CI], 0.52-0.85), rs17697515 (P = 0.001; OR, 0.62; CI, 0.47-0.81), and rs2333526 (P = 0.005; OR, 0.69; CI, 0.54-0.90). rs17697515 Was also specifically associated with DME in those with T2DM (P = 0.004; OR, 0.53; CI, 0.35-0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development. CONCLUSIONS: Significant associations were found between VEGFC tag SNPs (individually and within haplotypes) and the presence of any DR or DME in white participants with T1DM and T2DM. CI - Copyright (c) 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Kaidonis, Georgia AU - Kaidonis G AD - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. Electronic address: Georgia.Kaidonis@flinders.edu.au. FAU - Burdon, Kathryn P AU - Burdon KP AD - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia. FAU - Gillies, Mark C AU - Gillies MC AD - Save Sight Institute, Clinical Ophthalmology and Eye Health, the University of Sydney, Sydney, New South Wales, Australia. FAU - Abhary, Sotoodeh AU - Abhary S AD - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. FAU - Essex, Rohan W AU - Essex RW AD - Academic Unit of Ophthalmology, Australian National University, Canberra, Australia. FAU - Chang, John H AU - Chang JH AD - School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia; Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom. FAU - Pal, Bishwanath AU - Pal B AD - Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom. FAU - Pefkianaki, Maria AU - Pefkianaki M AD - Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom. FAU - Daniell, Mark AU - Daniell M AD - Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. FAU - Lake, Stewart AU - Lake S AD - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. FAU - Petrovsky, Nikolai AU - Petrovsky N AD - Department of Endocrinology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. FAU - Hewitt, Alex W AU - Hewitt AW AD - Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia. FAU - Jenkins, Alicia AU - Jenkins A AD - St Vincent's Hospital, Melbourne, Victoria, Australia. FAU - Lamoureux, Ecosse L AU - Lamoureux EL AD - Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia; Singapore Eye Research Institute, Singapore. FAU - Gleadle, Jonathan M AU - Gleadle JM AD - Department of Renal Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia. FAU - Craig, Jamie E AU - Craig JE AD - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150611 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (VEGFC protein, human) RN - 0 (Vascular Endothelial Growth Factor C) SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Cross-Sectional Studies MH - Diabetes Mellitus, Type 1/complications MH - Diabetes Mellitus, Type 2/complications MH - Diabetic Retinopathy/*genetics MH - Female MH - Genetic Variation MH - Genotyping Techniques MH - Humans MH - Macular Edema/*genetics MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Risk Factors MH - Sequence Tagged Sites MH - Vascular Endothelial Growth Factor C/*genetics MH - White People/genetics EDAT- 2015/06/15 06:00 MHDA- 2015/11/17 06:00 CRDT- 2015/06/15 06:00 PHST- 2015/02/12 00:00 [received] PHST- 2015/04/29 00:00 [revised] PHST- 2015/05/02 00:00 [accepted] PHST- 2015/06/15 06:00 [entrez] PHST- 2015/06/15 06:00 [pubmed] PHST- 2015/11/17 06:00 [medline] AID - S0161-6420(15)00429-7 [pii] AID - 10.1016/j.ophtha.2015.05.004 [doi] PST - ppublish SO - Ophthalmology. 2015 Sep;122(9):1828-36. doi: 10.1016/j.ophtha.2015.05.004. Epub 2015 Jun 11.