gms | German Medical Science

104th DOG Annual Meeting

21. - 24.09.2006, Berlin

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Complement factor H polymorphism, inflammation, smoking, and aging macular disease in the general population

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  • P. De Jong - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • D. Despriet - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • C. Klaver - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • A. Bergen - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • J. Witteman - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • I. Kardys - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • M. De Maat - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • S. Boekhoorn - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • J. Vingerling - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • A. Hofman - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • B. Oostra - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • A. Uitterlinden - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam
  • C. Van Duijn - Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam

Deutsche Ophthalmologische Gesellschaft e.V.. 104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft (DOG). Berlin, 21.-24.09.2006. Düsseldorf, Köln: German Medical Science; 2006. Doc06dogDO.02.09

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dog2006/06dog019.shtml

Published: September 18, 2006

© 2006 De Jong et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

To examine the recently reported association between aging macular disease (AMD) and the complement factor H (CFH) gene, a regulator of complement, in a large Caucasian population in conjunction with potentially modifying risk factors.

Methods

The frequency of the Y402H polymorphism of CFH was 36.2% in 5681 participants of the population-based Rotterdam Study. A diagnosis of early or late prevalent AMD at baseline and incident AMD after 7.6 years of follow-up was based on grading of fundus transparencies by the same graders according to the International Classification System. Risks of AMD were calculated according to the absence or presence of the CFH polymorphism. We next related these risks to serum markers of inflammation, smoking, and genetic variation of C-reactive protein (CRP).

Results

The odds ratio (OR) of AMD increased in an allele-dose manner with clinical severity from OR 2.71 (95% CI 2.10, 3.50) of early AMD , to OR 11.02 (6.82, 11.81) of late AMD for homozygous persons. Absolute risks of late AMD by age 95 were 21.9% for non-carriers of the CFH polymorphism, 42.6% for heterozygotes, and 48.3% for homozygotes. The population attributable risk of Y402H was 54.0%. Elevated erythrocyte sedimentation rates further increased risks to OR 20.2 (95% CI 9.5, 43.0), elevated serum CRP to OR 25.6 (9.8, 67.0), and smoking to OR 34.0 (13.0, 88.6) for homozygotes compared to non-carriers without these determinants. CRP haplotypes conferring high CRP levels further increased the effect of Y402H (P<0.008).

Conclusions

The CFH polymorphism Y402H accounts for the majority of AMD in the general population, and is particularly hazardous in the presence of environmental and genetic stimulators of the complement cascade.