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Abstract #92287 Published in IGR 22-1
Gene network analyses unveil possible molecular basis underlying drug-induced glaucoma
Ding RF; Yu Q; Liu K; Du J; Yin HJ; Ji ZLBMC Medical Genomics 2021; 14: 109
BACKGROUND: Drug-induced glaucoma (DIG) is a kind of serious adverse drug reaction that can cause irreversible blindness. Up-to-date, the molecular mechanism of DIG largely remains unclear yet due to the medical complexity of glaucoma onset. METHODS: In this study, we conducted data mining of tremendous historical adverse drug events and genome-wide drug-regulated gene signatures to identify glaucoma-associated drugs. Upon these drugs, we carried out serial network analyses, including the weighted gene co-expression network analysis (WGCNA), to illustrate the gene interaction network underlying DIG. Furthermore, we applied pathogenic risk assessment to discover potential biomarker genes for DIG. RESULTS: As the results, we discovered 13 highly glaucoma-associated drugs, a glaucoma-related gene network, and 55 glaucoma-susceptible genes. These genes likely played central roles in triggering DIGs via an integrative mechanism of phototransduction dysfunction, intracellular calcium homeostasis disruption, and retinal ganglion cell death. Further pathogenic risk analysis manifested that a panel of nine genes, particularly OTOF gene, could serve as potential biomarkers for early-onset DIG prognosis. CONCLUSIONS: This study elucidates the possible molecular basis underlying DIGs systematically for the first time. It also provides prognosis clues for early-onset glaucoma and thus assists in designing better therapeutic regimens.
State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, Fujian, People's Republic of China.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.2.2 Other risk factors for glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)
