CRP and sICAM–1 as Biomarkers in Age–Related Macular Degeneration

Abstract

Abstract: : Purpose: To evaluate whether CRP (C–Reactive Protein) and sICAM–1 (serum Intercellular Adhesion Molecule–1) biomarkers are independent risk factors for age–related macular degeneration (AMD) and to determine if known functional CRP gene polymorphisms affect CRP levels in AMD. Methods: 319 caucasian subjects with AMD and 442 normal controls, all over the age of 55 were recruited from ophthalmology clinics at the Southampton Eye Unit. AMD phenotypes were characterised by clinical examination, stereoscopic fundus photography, fluorescein angiography and optical coherence tomography. Serum CRP levels were measured using an automated clinical analyser and an sICAM–1 immunoassay was performed using a solid phase ELISA kit. Functional CRP gene polymorphisms +1444C/T and +1059G/C were analysed via a 5’ nuclease TaqMan^© PCR genotyping assay using the ABI 7900HT Sequence Detection System. Individuals reporting any infective illness in the preceding month or chronic joint and organ related inflammation were excluded from the CRP analysis. Case–control groups were analysed by logistic regression controlling for age, sex, body mass index and smoking status (current smokers and past smokers). Results: LogCRP values were significantly higher in AMD cases as compared to controls (P=0.002) on multivariate regression analysis. CRP values over 5 mg/l were strongly correlated with AMD (odds ratio=2.6, 95% CI=1.6 to 4.3, P=0.0001). The frequency of +1444 TT genotype was significantly lower in cases (6.2% vs. 11.2%, P=0.03), but neither +1444 nor + 1059 genotypes correlated with serum CRP levels. sICAM levels did not differ significantly in the two groups (mean levels = 301.5 vs. 271.8 units) but current smokers had significantly higher sICAM levels (P=0.0001). Conclusions: Elevated serum CRP > 5 mg/l is significantly associated with AMD. No correlation was observed between CRP polymorphisms +1444C/T and + 1059 G/C and serum CRP levels. sICAM levels do not predict AMD development but are raised in cigarette smokers.

Keywords: age-related macular degeneration • inflammation • genetics