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Ebony Liu, Georgia Kaidonis, Bennet McComish, Mark C Gillies, Sotoodeh Abhary, Mark Daniell, Nikolai Petrovsky, Jonathan Gleadle, Jamie E. Craig, Kathryn P Burdon; Genetic variants in microRNA genes and microRNA binding sites associated with diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3017. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Genetic variants in microRNA genes and microRNA binding sites have not been studied systematically in association with diabetic retinopathy (DR). We conducted a comprehensive search for single nucleotide polymorphisms (SNPs) in microRNA genes and microRNA binding sites utilizing data from a previous genome wide association study (GWAS) of Australian patients.
SNPs in microRNA genes and microRNA binding sites were obtained from the miRNASNP and PolymiRTS (version 2) online databases, and then imputed in cases and controls from our previous GWAS data using the Illumina OmniExpress array (n=1598). Analysis for association with DR and vision threatening DR (proliferative DR or clinically significant macula edema) were performed for type 1 and type 2 diabetes separately. Top ranking SNPs were selected by looking at their adjusted p values, odd ratios and significance in similar phenotype groups. These SNP were genotyped in a larger cohort that included the previous GWAS cohort (n=3694) to confirm their association with DR.
208 SNPs in microRNA genes and 41578 SNPs in microRNA binding sites were able to be imputed from the GWAS data. Most significant p-values adjusted for age, sex and HbA1c were less than 0.01 and 0.0001 for 16 microRNA SNPs and 18 microRNA binding site SNPs respectively, in relation to either the presence of DR or vision threatening DR compared with diabetic controls (no DR). None reached significance after Bonferroni correction. 46 top ranking SNPs were selected for subsequent genotyping in a larger cohort. SNPs selected included genes encoding upstream and downstream components of the NF-κB, TNFα, MAPK and VEGF pathways (LHX6, NLRP3, PCDH7, ALCAM, ADAMTS5, mir23A), endothelial cell adhesion and proliferation (GLG1, AFAP1) and immune system function (CD209, HLA-DPB1, MYSM1, CHST15).
A number of microRNA and microRNA binding sites in several highly relevant genes have been identified to be potentially significant in the development and severity of DR. These findings will be confirmed by genotyping the variants in a larger and more powerful cohort.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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