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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Identification of a novel mucin gene HCG22 associated with steroid-induced ocular hypertension
Investigative Ophthalmology and Visual Science, Volume 56, No. 4, Year 2015
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Description
PURPOSE. The pathophysiology of ocular hypertension (OH) leading to primary open-angle glaucoma shares many features with a secondary form of OH caused by treatment with glucocorticoids, but also exhibits distinct differences. In this study, a pharmacogenomics approach was taken to discover candidate genes for this disorder. METHODS. A genome-wide association study was performed, followed by an independent candidate gene study, using a cohort enrolled from patients treated with off-label intravitreal triamcinolone, and handling change in IOP as a quantitative trait. RESULTS. An intergenic quantitative trait locus (QTL) was identified at chromosome 6p21.33 near the 50 end ofHCG22 that attained the accepted statistical threshold for genome-level significance. The HCG22 transcript, encoding a novel mucin protein, was expressed in trabecular meshwork cells, and expression was stimulated by IL-1, and inhibited by triamcinolone acetate and TGF-b. Bioinformatic analysis defined the QTL as an approximately 4 kilobase (kb) linkage disequilibrium block containing 10 common single nucleotide polymorphisms (SNPs). Four of these SNPs were identified in the National Center for Biotechnology Information (NCBI) GTEx eQTL browser as modifiers of HCG22 expression.Most are predicted to disrupt or improvemotifs for transcription factor binding, themost relevant being disruption of the glucocorticoid receptor bindingmotif. A second QTL was identified within the predicted signal peptide of the HCG22 encoded protein that could affect its secretion. Translation, O-glycosylation, and secretion of the predicted HCG22 protein was verified in cultured trabecular meshwork cells. CONCLUSIONS. Identification of two independent QTLs that could affect expression of the HCG22 mucin gene product via two different mechanisms (transcription or secretion) is highly suggestive of a role in steroid-induced OH. © 2015 The Association for Research in Vision and Ophthalmology, Inc.
Authors & Co-Authors
Edlund, Christopher K.
United States, Los Angeles
University of Southern California
Hartiala, Jaana A.
United States, Los Angeles
University of Southern California
Hazelett, Dennis J.
United States, Los Angeles
Keck School of Medicine of Usc
Davis, Janet L.
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Flynn, Harry W.
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Allayee, Hooman
United States, Los Angeles
University of Southern California
Coetzee, Gerhard A.
United States, Los Angeles
University of Southern California
United States, Los Angeles
Keck School of Medicine of Usc
Conti, David V.
United States, Los Angeles
University of Southern California
Schwartz, Stephen G.
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Statistics
Citations: 23
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1167/iovs.14-14803
ISSN:
01460404
Research Areas
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases
Study Design
Cohort Study
Study Approach
Quantitative