title: A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
authors.forename: Annie K
authors.initials: AK
authors.lastname: McAuley
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Dirani
authors.affiliation: 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.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Connell
authors.affiliation: 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.
authors.forename: Ecosse L
authors.initials: EL
authors.lastname: Lamoureux
authors.affiliation: 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.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014785:Vision, Ocular / Q000235:genetics*
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs
keywords: Diabetic retinopathy; miR-126; microRNA; microvasculature; single nucleotide polymorphism