Liu, E and Kaidonis, G and McComish, BJ and Gillies, MC and Abhary, S and Essex, RW and Chang, JH and Pal, B and Daniell, M and Lake, S and Petrovsky, N and Hewitt, AW and Jenkins, A and Lamoureux, EL and Gleadle, JM and Craig, JE and Burdon, KP, MicroRNA-related genetic variants are associated with diabetic retinopathy in type 1 diabetes mellitus, Investigative Ophthalmology & Visual Science, 60, (12) pp. 3937-3942. ISSN 1552-5783 (2019) [Refereed Article]
Copyright 2019 The Authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/
Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR.
Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size.
Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.
|Item Type:||Refereed Article|
|Keywords:||diabetic retinopathy, microRNA, genetic variants, type 1 diabetes, Caucasian|
|Research Division:||Medical and Health Sciences|
|Research Group:||Clinical Sciences|
|Research Field:||Medical Genetics (excl. Cancer Genetics)|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|UTAS Author:||McComish, BJ (Dr Bennet McComish)|
|UTAS Author:||Hewitt, AW (Professor Alex Hewitt)|
|UTAS Author:||Burdon, KP (Professor Kathryn Burdon)|
|Deposited By:||Menzies Institute for Medical Research|
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