Annie K McAuley1, Mohamed Dirani1, Jie Jin Wang2, Paul P Connell3, Ecosse L Lamoureux4, Alex W Hewitt5. 1. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia. 2. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia. 3. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Mater Misericordiae University Hospital, Dublin, Ireland. 4. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Singapore Eye Research Institute, National University of Singapore, Singapore DUKE-NUS Graduate Medical School, Office of Clinical Sciences, Singapore. 5. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, WA, Australia hewitt.alex@gmail.com.
Abstract
BACKGROUND: The regulation of miR-126 by rs4636297 single nucleotide polymorphism (SNP) has been implicated in the pathogenesis of neovascularisation by promoting vascular endothelial growth factor, suggesting it could be associated with sight threatening diabetic retinopathy (STDR), but has not been previously investigated or reported. MATERIALS AND METHODS: A case control study of 531 individuals with diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold chemistry. STDR included people with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was tested using logistic regression analysis, adjusting for confounding variables. RESULTS: In an additive model, the A allele of rs4636297 SNP is significantly associated with STDR compared to people with none or mild diabetic retinopathy (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p = 0.006). CONCLUSION: The A allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR.
BACKGROUND: The regulation of miR-126 by rs4636297 single nucleotide polymorphism (SNP) has been implicated in the pathogenesis of neovascularisation by promoting vascular endothelial growth factor, suggesting it could be associated with sight threatening diabetic retinopathy (STDR), but has not been previously investigated or reported. MATERIALS AND METHODS: A case control study of 531 individuals with diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold chemistry. STDR included people with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was tested using logistic regression analysis, adjusting for confounding variables. RESULTS: In an additive model, the A allele of rs4636297 SNP is significantly associated with STDR compared to people with none or mild diabetic retinopathy (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p = 0.006). CONCLUSION: The A allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR.
Authors: Dorothee Kaudewitz; Philipp Skroblin; Lukas H Bender; Temo Barwari; Peter Willeit; Raimund Pechlaner; Nicholas P Sunderland; Karin Willeit; Allison C Morton; Paul C Armstrong; Melissa V Chan; Ruifang Lu; Xiaoke Yin; Filipe Gracio; Katarzyna Dudek; Sarah R Langley; Anna Zampetaki; Emanuele de Rinaldis; Shu Ye; Timothy D Warner; Alka Saxena; Stefan Kiechl; Robert F Storey; Manuel Mayr Journal: Circ Res Date: 2015-12-08 Impact factor: 17.367