March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Genetic Association of Glucose Transporter Type 1 Variants with Age-Related Macular Degeneration and its Direct Interaction with Complement Factor H at the Protein Level
Elod Kortvely; Anneke I. Den Hollander; Matteo Gorza; Valentina Cipriani; John R. Yates; Caroline Hayward; Alan F. Wright; Sascha Fauser; Carel C. Hoyng; Marius Ueffing
Author Affiliations & Notes
  • Elod Kortvely
    Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany
  • Anneke I. Den Hollander
    Department of Ophthalmology, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands
  • Matteo Gorza
    Research Unit for Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • Valentina Cipriani
    Institute of Ophthalmology, University College, London, London, United Kingdom
  • John R. Yates
    Institute of Ophthalmology, University College, London, London, United Kingdom
    Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom
  • Caroline Hayward
    Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh, United Kingdom
  • Alan F. Wright
    Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh, United Kingdom
  • Sascha Fauser
    University Eye Hospital Cologne, Cologne, Germany
  • Carel C. Hoyng
    Department of Ophthalmology, Radboud University Nijmegen, Medical Centre, Nijmegen, The Netherlands
  • Marius Ueffing
    Research Unit for Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    Institute for Ophthalmic Research, University Eye Hospital, Tuebingen, Germany
  • Footnotes
    Commercial Relationships  Elod Kortvely, None; Anneke I. Den Hollander, None; Matteo Gorza, None; Valentina Cipriani, None; John R. Yates, None; Caroline Hayward, None; Alan F. Wright, None; Sascha Fauser, None; Carel C. Hoyng, None; Marius Ueffing, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6483. doi:
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      Elod Kortvely, Anneke I. Den Hollander, Matteo Gorza, Valentina Cipriani, John R. Yates, Caroline Hayward, Alan F. Wright, Sascha Fauser, Carel C. Hoyng, Marius Ueffing; Genetic Association of Glucose Transporter Type 1 Variants with Age-Related Macular Degeneration and its Direct Interaction with Complement Factor H at the Protein Level. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6483.

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Abstract

Purpose: : Mutations and polymorphic variants in complement factor H (CFH), the main inhibitor of the alternative complement pathway, have been found to be associated with age-related macular degeneration (AMD). In the present study, we sought to identify proteins interacting with CFH that could provide new insights into its (patho)physiological function.

Methods: : A yeast two-hybrid screen was performed using the non-risk variant of CFH as bait against a human placental cDNA library, in order to identify direct interacting partners. The physiological interaction was confirmed by co-immunoprecipitation followed by mass spectrometry. Glucose transporter type 1 (GLUT1/SLC2A1), a protein identified with both methods as a binding partner of CFH, was selected for further genetic association analysis. Nine tag SNPs were genotyped in three independent cohorts including 1,888 AMD patients and 954 healthy controls.

Results: : Using yeast two-hybrid analysis we found that CFH directly binds to GLUT1, the key glucose transporter of the blood-retina barrier. The physical interaction was also confirmed by co-immunoprecipitation experiments combined with mass spectrometry. Further analyses suggest that GLUT1 engages CFH in retinal pigment epithelium cells via its C-terminal exomembrane domains. Genetic association studies detected a significant correlation of GLUT1 polymorphisms (SNP rs3768029) with AMD. Compared to the reference CC-genotype, ORs of 1.339 (95% CI=1.113-1.611, p=0.001) and 1.344 (95% CI=1.067-1.694, p=0.01) were obtained for carriers with CT- and TT-genotypes, respectively.

Conclusions: : These results demonstrate a new role for GLUT1 in the localization of CFH to the blood-retina barrier. Polymorphisms in the GLUT1 gene may contribute to AMD risk.

Keywords: age-related macular degeneration • protein structure/function • linkage analysis 
© 2012, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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