May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Complement Component C3 and Risk of Age-Related Macular Degeneration
Author Affiliations & Notes
  • C. C. Klaver
    Erasmus Medical Center, Rotterdam, The Netherlands
    Ophthalmology, Ophthalmogenetics,
    NIN, Amsterdam, The Netherlands
  • D. D. G. Despriet
    Erasmus Medical Center, Rotterdam, The Netherlands
    Ophthalmology, Ophthalmogenetics,
    NIN, Amsterdam, The Netherlands
  • C. van Duijn
    Erasmus Medical Center, Rotterdam, The Netherlands
    Epidemiology,
  • P. T. V. M. de Jong
    Erasmus Medical Center, Rotterdam, The Netherlands
    Ophthalmology, Ophthalmogenetics,
    NIN, Amsterdam, The Netherlands
  • J. R. Vingerling
    Erasmus Medical Center, Rotterdam, The Netherlands
    Ophthalmology, Ophthalmogenetics,
  • A. A. B. Bergen
    Ophthalmology, Ophthalmogenetics,
    NIN, Amsterdam, The Netherlands
  • Footnotes
    Commercial Relationships  C.C. Klaver, None; D.D.G. Despriet, None; C. van Duijn, None; P.T.V.M. de Jong, None; J.R. Vingerling, None; A.A.B. Bergen, None.
  • Footnotes
    Support  Henkes stichting, EUR fellowship, Stichting Swart van Essen
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2663. doi:https://doi.org/
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      C. C. Klaver, D. D. G. Despriet, C. van Duijn, P. T. V. M. de Jong, J. R. Vingerling, A. A. B. Bergen; Complement Component C3 and Risk of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2663. doi: https://doi.org/.

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

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Abstract

Purpose: : To explore the association between the R102G and P314L polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of CFH Y402H, LOC387715 A69S and smoking.

Methods: : We genotyped all study participants from the prospective, population-based Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations between September 1, 1993, and December 31, 2004; N=6418) and an independent case-control study from the Netherlands (357 cases; 173 controls) for the two risk alleles in C3. Early and late stages of prevalent and incident AMD were graded according to the international classification and grading system for AMD. Information on cigarette smoking was obtained by interview at baseline.

Results: : We found a population frequency of 0.217 for R102G and 0.211 for P314L in the Rotterdam Study. Both alleles significantly increased the risk of early AMD and all subtypes of late AMD, and this risk appeared independent of CFH Y402H, LOC387715 A69S, and smoking. Detailed analysis showed that the haplotype carrying both alleles had the highest frequency difference between cases and controls (P=0.006). We estimated a total population-attributable risk of 14.6%. Meta-analysis on all currently available data yielded a pooled odds ratio (OR) 1.61 (95%CI 1.46-1.78) for the R102G allele, and OR 1.50 (95%CI 1.31-1.71) for the P314L allele.

Conclusions: : These findings further highlight the significant role of the complement pathway in the etiology of AMD.

Keywords: age-related macular degeneration • genetics • clinical (human) or epidemiologic studies: risk factor assessment 
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