Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Autor:	Rämö JT; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.; Massachusetts Eye and Ear, Boston, MA, USA.; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA., Gorman B; Center for Data and Computational Sciences (C-DACS), VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.; Booz Allen Hamilton, McLean, VA, USA., Weng LC; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Jurgens SJ; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Department of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Singhanetr P; Massachusetts Eye and Ear, Boston, MA, USA.; Mettapracharak Eye Institute, Mettapracharak (Wat Rai Khing) Hospital, Nakhon Pathom, Thailand., Tieger MG; New England Eye Center, Tufts Medical Center, Boston, MA, USA., van Dijk EH; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Halladay CW; Center of Innovation in Long Term Services and Supports, Providence VA Medical Center, Providence, RI, USA., Wang X; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Brinks J; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Choi SH; Department of Biostatistics, Boston University, Boston, MA, USA., Luo Y; Massachusetts Eye and Ear, Boston, MA, USA., Pyarajan S; VA Cooperative Studies Program, VA Boston Healthcare System, Boston, MA, USA.; Department of Medicine, Brigham and Women's Hospital and Harvard School of Medicine, Boston, MA, USA., Nealon CL; Eye Clinic, VA Northeast Ohio Healthcare System, Cleveland, OH, USA., Gorin MB; Department of Ophthalmology, David Geffen School of Medicine, Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Human Genetics, David Geffen School of Medicine, Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA, USA., Wu WC; Section of Cardiology, Medical Service, VA Providence Healthcare System, Providence, RI, USA., Sobrin L; Harvard Medical School Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA., Kaarniranta K; Department of Ophthalmology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland., Yzer S; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Palotie A; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Peachey NS; Research Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.; Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA., Turunen JA; Folkhälsan Research Center, Biomedicum, Helsinki, Finland.; Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Boon CJ; Department of Ophthalmology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands., Ellinor PT; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Iyengar SK; Research Service, VA Northeast Ohio Healthcare System, Cleveland, OH, USA.; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Daly MJ; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Rossin EJ; Harvard Medical School Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 May 09. Date of Electronic Publication: 2024 May 09.
DOI:	10.1101/2024.05.08.24307013
Abstrakt:	Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10 -9 ). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10 -15 ). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10 -4 ) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10 -11 ) and glaucoma (OR=0.82, P=6.9×10 -9 ). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases. Competing Interests: Declaration of Competing Interests Dr. Rossin and Dr. Rämö are named inventors on a provisional patent application that describes the secondary use of intravitreal Anti-Ang2 medications for use in the treatment of central serous chorioretinopathy. Dr. Ellinor receives sponsored research support from Bayer AG, IBM Research, Bristol Myers Squibb, Pfizer and Novo Nordisk; he has also served on advisory boards or consulted for MyoKardia and Bayer AG. The remaining authors declare no competing interests.
Databáze:	MEDLINE
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