C-reactive protein levels and complement factor H polymorphism interaction in age-related macular degeneration and its progression.
OBJECTIVE
To determine the effect of elevated level of C-reactive protein (CRP) and its joint effect with the complement factor H (CFH) polymorphism on prevalent age-related macular degeneration (AMD) and its progression.


METHODS
Two-arm case-control study: (a) Study on prevalent AMD cases and population-based controls; (b) longitudinal study on AMD progression, comparing those in whom AMD progressed with those with no progression.


METHODS
(a) A cross-sectional sample of 544 participants, of whom 312 had features of early or late AMD and 232 were controls; (b) a sample of 254 early AMD cases, followed for 7 years.


METHODS
The study was conducted in Melbourne, Australia. Macular stereo photographs were graded for AMD according to the International Classification and Grading System. High-sensitivity CRP was measured in fresh serum, and genotyping was performed through the Australian Genome Research Facility. The association of CRP with outcomes was tested using multivariate logistic regression analysis adjusted for age, smoking, anti-inflammatory medications, and the CC genotype of the CFH gene. Risk factor interaction was explored using an additive model.


METHODS
Prevalent early AMD, prevalent late AMD, progressed AMD, and measures of risk factor interaction.


RESULTS
Elevated CRP levels were associated with late AMD: odds ratio (OR), 3.12; 95% confidence interval (CI), 1.38-7.07. An association of elevated CRP with AMD progression was weaker: OR, 1.90 (95% CI, 0.88-4.10). A combination of elevated CRP and the CC (Y402H) genotype resulted in a super-additivity of the risks, with odds ratios of 19.3 (95% CI, 2.8-134) for late AMD, and 6.8 (95% CI, 1.2-38.8) for AMD progression, with the attributable proportion of risk owing to CRP-CFH interaction calculated at 26% for prevalent late AMD and 22% for AMD progression.


CONCLUSIONS
Synergistic influence of CRP levels and the at risk genotype of the CFH gene resulted in a super-additive risk for prevalent late AMD and AMD progression. Testing for the combination of these 2 risk factors to predict a high risk of AMD and its progression would allow for targeted trials of new intervention strategies.
Robman
Luba
L
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. liubov@unimelb.edu.au
Baird
Paul N
PN
Dimitrov
Peter N
PN
Richardson
Andrea J
AJ
Guymer
Robyn H
RH
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
C493495:CFH protein, human; D017242:Complement Factor H; D002097:C-Reactive Protein