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Abstract #69468 Published in IGR 18-1
A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium
Liu Y; Bailey JC; Helwa I; Dismuke WM; Cai J; Drewry M; Brilliant MH; Budenz DL; Christen WG; Chasman DI; Fingert JH; Gaasterland D; Gaasterland T; Gordon MO; Igo RP; Kang JH; Kass MA; Kraft P; Lee RK; Lichter P; Moroi SE; Realini A; Richards JE; Ritch R,Investigative Ophthalmology and Visual Science 2016; 57: 3974-3981
PURPOSE: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG). METHODS: Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls. RESULTS: Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment. CONCLUSIONS: Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.
Department of Cellular Biology and Anatomy Augusta University, Augusta, Georgia, United States 2James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States 3Center for Biotechnology and Genomic Medicine, Augusta Uni.
Full articleClassification:
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
