Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema

Georgia Kaidonis; Kathryn P Burdon; Mark C Gillies; Sotoodeh Abhary; Rohan W Essex; John H Chang; Bishwanath Pal; Maria Pefkianaki; Mark Daniell; Stewart Lake; Nikolai Petrovsky; Alex W Hewitt; Alicia Jenkins; Ecosse L Lamoureux; Jonathan M Gleadle; Jamie E Craig

doi:10.1016/j.ophtha.2015.05.004

Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema

Ophthalmology. 2015 Sep;122(9):1828-36. doi: 10.1016/j.ophtha.2015.05.004. Epub 2015 Jun 11.

Authors

Georgia Kaidonis¹, Kathryn P Burdon², Mark C Gillies³, Sotoodeh Abhary⁴, Rohan W Essex⁵, John H Chang⁶, Bishwanath Pal⁷, Maria Pefkianaki⁷, Mark Daniell⁸, Stewart Lake⁴, Nikolai Petrovsky⁹, Alex W Hewitt¹⁰, Alicia Jenkins¹¹, Ecosse L Lamoureux¹², Jonathan M Gleadle¹³, Jamie E Craig⁴

Affiliations

¹ Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. Electronic address: Georgia.Kaidonis@flinders.edu.au.
² Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
³ Save Sight Institute, Clinical Ophthalmology and Eye Health, the University of Sydney, Sydney, New South Wales, Australia.
⁴ Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
⁵ Academic Unit of Ophthalmology, Australian National University, Canberra, Australia.
⁶ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia; Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
⁷ Medical Retina Service, Moorfields Eye Hospital, London, United Kingdom.
⁸ Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁹ Department of Endocrinology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
¹⁰ Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
¹¹ St Vincent's Hospital, Melbourne, Victoria, Australia.
¹² Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia; Singapore Eye Research Institute, Singapore.
¹³ Department of Renal Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia.

PMID: 26072347
DOI: 10.1016/j.ophtha.2015.05.004

Abstract

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.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 1 / complications
Diabetes Mellitus, Type 2 / complications
Diabetic Retinopathy / genetics*
Female
Genetic Variation
Genotyping Techniques
Humans
Macular Edema / genetics*
Male
Middle Aged
Polymorphism, Single Nucleotide*
Risk Factors
Sequence Tagged Sites
Vascular Endothelial Growth Factor C / genetics*
White People / genetics

Substances

VEGFC protein, human
Vascular Endothelial Growth Factor C