دورية أكاديمية
Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.
| العنوان: | Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus. |
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| المؤلفون: | Williams BL; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Zouache MA; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Seager NA; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Pappas CM; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Liu J; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Anstadt RA; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Hubbard WC; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Thomas J; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Hageman JL; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Mohler J; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Richards BT; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States., Hageman GS; Sharon Eccles Steele Center for Translational Medicine, John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, Utah, United States. |
| المصدر: | Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Apr 01; Vol. 65 (4), pp. 34. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Association For Research In Vision And Ophthalmology (Arvo) Country of Publication: United States NLM ID: 7703701 Publication Model: Print Cited Medium: Internet ISSN: 1552-5783 (Electronic) Linking ISSN: 01460404 NLM ISO Abbreviation: Invest Ophthalmol Vis Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo) Original Publication: St. Louis, Mosby. |
| مواضيع طبية MeSH: | High-Temperature Requirement A Serine Peptidase 1*/blood , High-Temperature Requirement A Serine Peptidase 1*/genetics , High-Temperature Requirement A Serine Peptidase 1*/metabolism , Macular Degeneration*/genetics , Macular Degeneration*/metabolism , Macular Degeneration*/diagnosis , Serine Endopeptidases*/genetics , Serine Endopeptidases*/metabolism , Vitreous Body*/metabolism, Aged ; Female ; Humans ; Male ; Chromosomes, Human, Pair 10/genetics ; Enzyme-Linked Immunosorbent Assay/methods ; Genetic Predisposition to Disease ; Risk Factors ; Sensitivity and Specificity |
| مستخلص: | Purpose: The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process. Methods: A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively. Results: The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05). Conclusions: HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus. |
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| معلومات مُعتمدة: | R24 EY017404 United States EY NEI NIH HHS |
| المشرفين على المادة: | EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1) EC 3.4.21.- (HTRA1 protein, human) EC 3.4.21.- (Serine Endopeptidases) |
| تواريخ الأحداث: | Date Created: 20240422 Date Completed: 20240429 Latest Revision: 20240509 |
| رمز التحديث: | 20240509 |
| مُعرف محوري في PubMed: | PMC11044837 |
| DOI: | 10.1167/iovs.65.4.34 |
| PMID: | 38648039 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1552-5783 |
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| DOI: | 10.1167/iovs.65.4.34 |