Journal article
Myocilin Mutations in Patients With Normal-Tension Glaucoma
JAMA ophthalmology, Vol.137(5), pp.559-563
05/01/2019
DOI: 10.1001/jamaophthalmol.2019.0005
PMCID: PMC6512256
PMID: 30816940
Abstract
Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated.\nTo evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG.\nIn this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018.\nComparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test.\nOf 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P = .03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P = .15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P = .04).\nIn cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.
Details
- Title: Subtitle
- Myocilin Mutations in Patients With Normal-Tension Glaucoma
- Creators
- Wallace L M Alward - Institute for Vision Research, University of Iowa, Iowa CityCarly van der Heide - Institute for Vision Research, University of Iowa, Iowa CityCheryl L Khanna - Department of Ophthalmology, Mayo Clinic, Rochester, MinnesotaBen R Roos - Institute for Vision Research, University of Iowa, Iowa CitySobha Sivaprasad - Kings College Hospital, London, EnglandJason Kam - Kaiser Permanente, Seattle, WashingtonRobert Ritch - Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New YorkAndrew Lotery - Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, EnglandRobert P Igo Jr - Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OhioJessica N Cooke Bailey - Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OhioEdwin M Stone - Institute for Vision Research, University of Iowa, Iowa CityTodd E Scheetz - Institute for Vision Research, University of Iowa, Iowa CityYoung H Kwon - Institute for Vision Research, University of Iowa, Iowa CityLouis R Pasquale - Massachusetts Eye and Ear Infirmary, Harvard University, BostonJaney L Wiggs - Massachusetts Eye and Ear Infirmary, Harvard University, BostonJohn H Fingert - Institute for Vision Research, University of Iowa, Iowa City
- Resource Type
- Journal article
- Publication Details
- JAMA ophthalmology, Vol.137(5), pp.559-563
- Publisher
- United States
- DOI
- 10.1001/jamaophthalmol.2019.0005
- PMID
- 30816940
- PMCID
- PMC6512256
- ISSN
- 2168-6165
- eISSN
- 2168-6173
- Grant note
- R01 EY015473 / NEI NIH HHS\nR01 EY023512 / NEI NIH HHS\nU01 HG004728 / NHGRI NIH HHS\nR01 EY023242 / NEI NIH HHS\nR21 EY028671 / NEI NIH HHS\nT32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070162402771
Metrics
14 Record Views