May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Y402H Polymorphism of Complement Factor H Affects Binding Affinity to C-Reactive Protein
Author Affiliations & Notes
  • I. J. Immonen
    Helsinki University Hospital, Helsinki, Finland
    Ophthalmology,
  • M. Laine
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • H. Jarva
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • S. Seitsonen
    Helsinki University Hospital, Helsinki, Finland
    Ophthalmology,
  • K. Haapasalo
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • M. J. Lehtinen
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • N. Lindeman
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • I. Järvelä
    Helsinki University Hospital, Helsinki, Finland
    Laboratory of Molecular Genetics,
  • S. Jokiranta
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • S. Meri
    Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
  • Footnotes
    Commercial Relationships I.J. Immonen, None; M. Laine, None; H. Jarva, None; S. Seitsonen, None; K. Haapasalo, None; M.J. Lehtinen, None; N. Lindeman, None; I. Järvelä, None; S. Jokiranta, None; S. Meri, None.
  • Footnotes
    Support Sohlberg , Instru, Paulo and Silmäsäätiö foundations
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2176. doi:https://doi.org/
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      I. J. Immonen, M. Laine, H. Jarva, S. Seitsonen, K. Haapasalo, M. J. Lehtinen, N. Lindeman, I. Järvelä, S. Jokiranta, S. Meri; Y402H Polymorphism of Complement Factor H Affects Binding Affinity to C-Reactive Protein. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2176. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Y402H polymorphism of the complement factor H (FH) is a powerful risk factor for age-related macular degeneration (AMD). Since the Y402H occurs at the C-reactive protein binding region of the FH, we wanted to evaluate the the effect of the Y402H polymorphism on the interaction between FH and CRP at the protein level.

Methods:: Serum FH and purified serum FH from AMD patients and control subjects with the normal genotype (TT) and from those homo- or heterotzygous (TT or CT) for the Y402H polymorphism was tested for binding into CRP-coated plate wells. In addition normal and Y402H recombinant constructs of the SCR5-7 fragments of FH were tested for CRP binding.

Results:: FH from sera of of AMD patients with the CC genotype showed a strongly reduced binding to CRP (0.369+0.102 U) compared to patients with the TT genotype (0.532+0.102 U). A similar difference was observed in age-mathed control subjects with the corresponding genotypes.Full length variants of FH purified from sera of subjects with the CC genotypes exhibited a weaker binding to CRP (0.470+ 0.033 U) compared to those of the TT genotype (0.688+0.103 U). An even more marked difference in CRP binding was observed between the recombinant FH SCR 5-7 402H or 402Yfragments (0.300 vs 0.05 U, correspondingly).

Conclusions:: Y402H polymorphism interferes with CRP binding of serum FH.Since the decreased binding was detected also in SCR 5-7 constructs, the decrase was not solely due to the 3-dimensional configuration change predicted to occur in the FH molecule in Y402H polymorphism.The decrease in CRP binding was similar in AMD patients and in healthy controls with the polymorphism.

Keywords: age-related macular degeneration • genetics • proteins encoded by disease genes 
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