In participants with intermediate-stage AMD at enrollment in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and 2:1 controls matched for age and sex, cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP).Main outcome measure was mortality.
In this review, we will address recent evidence that links CRP and AMD pathogenesis, which may open new therapeutic opportunities to prevent the progression of AMD.
There is a considerable body of evidence demonstrating a link between the membrane attack complex (MAC) and age-related macular degeneration (AMD), and between C-reactive protein (CRP) and AMD.
Furthermore, we discuss the complement system as it relates to AMD pathophysiology, provide a model for the role of CRP in this disease, and outline current therapies being developed and tested to treat AMD patients.
We calculated relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) to clarify possible interaction of different genotypes and CRP levels for AMD.
C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE.
Previous studies have suggested a link between elevated levels of total C-reactive protein (CRP) in the choroid, CFH genotype, and AMD status; however, the structural form of CRP present in the choroid, its relationship to CFH genotype, and its functional consequences have not been assessed.
Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD.
To investigate the influence of the Factor H (CFH) Tyr⁴⁰²His polymorphism on the plasma levels of the alternative pathway proteins CFH, C3, Factor B (FB), Factor D (FD), and Factor I (FI) and the inflammatory marker C-reactive protein (CRP) in 119 patients with age-related macular degeneration (AMD) and 152 unrelated control individuals.
The SCR-16/20 site is novel and indicates the importance of the FH-CRP interaction for both age-related macular degeneration and atypical hemolytic uremic syndrome.
The FH-CRP interaction is only observed when native CRP is at high acute-phase concentration levels, and CRP binds weakly to the His402 FH allotype to suggest a molecular mechanism that leads to AMD.
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.
Single nucleotide polymorphisms (SNPs) in both genes were also independently associated with risk of AMD, controlling for the level of CRP and other factors.
Our data did not show significant association between the CFH Y402H polymorphism and PDT treatment response for neovascular AMD; however, CRP genetic variants were associated with a positive response to PDT treatment for neovascular AMD.
The purpose of this study was to understand how the Y402H variant in FH/FHL-1 contributes to the pathogenesis of AMD and, in particular, whether interactions mediated by FH/FHL-1, including binding to C-reactive protein (CRP), group A streptococcal M protein (GAS M6), heparin, and retinal pigment epithelial cells (RPE), are affected.
We provide evidence that if elevated serum/plasma levels of CRP are associated with neovascular AMD, it is likely not due to genetic variation within CRP, but likely due to variations in some other genetic as well as epidemiological factors.
Combined effects on the likelihood of early or late AMD were demonstrated for the LOC387715 Ala69Ser G/T and T/T genotypes with the markers high-sensitivity CRP (odds ratios [ORs], 1.2 for the highest tertile alone, 1.6 for G/T and T/T genotypes alone, and 2.2 for both G/T and T/T genotypes plus the highest tertile, compared with the G/G genotype with the 2 lower tertiles), IL-6 (corresponding ORs, 1.1, 1.6, and 2.2), sICAM-1 (ORs, 1.0, 1.5, and 2.3, respectively), and PAI-1 (ORs, 1.3, 1.7, and 2.3, respectively), but not with WCC, fibrinogen, homocysteine, and von Willebrand factor.
Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points.