title: A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients.
abstract: OBJECTIVE
  This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus.
  
  
  METHODS
  Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension.
  
  
  RESULTS
  A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23-3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83-1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03-1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54-1.42); P = 0.583), or with PDR for either type of DM.
  
  
  CONCLUSIONS
  Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia. georgia.kaidonis@gmail.com.
authors.forename: Georgia
authors.identifier: http://orcid.org/0000-0002-7558-0607
authors.initials: G
authors.lastname: Kaidonis
authors.affiliation: Save Sight Institute, Clinical Ophthalmology and Eye Health, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gillies
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia.
authors.forename: Sotoodeh
authors.initials: S
authors.lastname: Abhary
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia.
authors.forename: Ebony
authors.initials: E
authors.lastname: Liu
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 NSW, Sydney, NSW, Australia.|Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: Bishwanath
authors.initials: B
authors.lastname: Pal
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: Sobha
authors.initials: S
authors.lastname: Sivaprasad
authors.affiliation: Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Pefkianaki
authors.affiliation: Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Daniell
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia.
authors.forename: Stewart
authors.initials: S
authors.lastname: Lake
authors.affiliation: Department of Endocrinology, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: St Vincent's Hospital, Melbourne, VIC, Australia.
authors.forename: Alicia
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia.|Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: Ecosse L
authors.initials: EL
authors.lastname: Lamoureux
authors.affiliation: Department of Renal Medicine, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gleadle
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia.|Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008269:Macular Edema / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; C542542:MIRN146 microRNA, human; D035683:MicroRNAs
keywords: Diabetic macular oedema; Diabetic nephropathy; Diabetic retinopathy; Genetics; microRNA; microRNA-146a