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L. Robman, P. N. Baird, A. J. Richardson, P. N. Dimitrov, R. H. Guymer; Interaction of Inflammatory and Genetic Risks for Prevalent AMD and AMD Progression. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1665.
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To test two AMD risk factors: elevated level of C-reactive protein (CRP) and the CC risk genotype of the Y402H variant of the CFH gene for their interaction in relation to prevalent AMD and AMD progression
The interactive effect was assessed in individuals from the Cardiovascular Health and Age-related Maculopathy (CHARM) study that had both cross-sectional and longitudinal arms. The Interaction Contrast Ratio (ICR), Attributable Proportion (AP) and Synergy Index (S) for these two factors were estimated as measures of their possible interaction.
Out of 544 participants in the cross-sectional sample 38 had late AMD, 219 had drusen of size 63 microns or larger, 55 had pigmentary abnormalities only and 232 were controls. 90(16.5%) participants had elevated CRP level, and 92(16.9%) participants had the risk CC genotype. Combination of these two risk factors resulted in an increased the odds ratio for late AMD to 19.3 (p<0.003), adjusted for age, smoking and use of anti-inflammatory drugs, due to an excessive risk caused by a synergistic effect, with all measures of interaction departing from additivity: ICR=1.36, AP=0.26, and S=2.39. No association of CRP level with early AMD was detected.Out of 222 early AMD participants in the longitudinal cohort, in 74 (33%) disease progressed. 36(16%) participants had an elevated CRP level and 40 (18%) participants carried the risk CC genotype of Y402H, which has been shown previously to be associated with AMD progression in this study.1 A 7-fold increased risk of progression (p<0.03), controlled for age, smoking, time of follow up and use of anti-inflammatory drugs, was evident when a combination of the CC genotype and elevated CRP level were present. An interactive effect suggested synergy, with ICR=0.56, AP=0.22, and S=6.12.
Genetic and inflammatory risk factors for AMD produced a super-additive effect towards an increased prevalence of late AMD and risk of AMD progression that was in excess to the net sum of the risks from these two factors when considered separately. Stratification of the AMD population by AMD- genotypes and risk factor profile combinations could be used to detect a high risk sub population with a greater vulnerability to AMD progression and visual loss from late AMD.1 Baird P, Robman L, Richardson A, et al. Hum Mol Genetics. 2008;17:1299-305
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