title: Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  Cross-sectional, case control study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. Electronic address: Georgia.Kaidonis@flinders.edu.au.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kaidonis
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Save Sight Institute, Clinical Ophthalmology and Eye Health, the University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gillies
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Sotoodeh
authors.initials: S
authors.lastname: Abhary
authors.affiliation: Academic Unit of Ophthalmology, Australian National University, Canberra, Australia.
authors.forename: Rohan W
authors.initials: RW
authors.lastname: Essex
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia; Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: John H
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Bishwanath
authors.initials: B
authors.lastname: Pal
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Pefkianaki
authors.affiliation: Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Daniell
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Stewart
authors.initials: S
authors.lastname: Lake
authors.affiliation: Department of Endocrinology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: St Vincent's Hospital, Melbourne, Victoria, Australia.
authors.forename: Alicia
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia; Singapore Eye Research Institute, Singapore.
authors.forename: Ecosse L
authors.initials: EL
authors.lastname: Lamoureux
authors.affiliation: Department of Renal Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gleadle
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D060005:Genotyping Techniques; D006801:Humans; D008269:Macular Edema / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016324:Sequence Tagged Sites; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C