Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration

Importance C-reactive protein (CRP) is a circulating inflammatory marker associated with late age-related macular degeneration (AMD). It remains uncertain whether the association between CRP concentrations and AMD is causal. Objective To assess whether CRP (OMIM123260) single-nucleotide polymorphisms that influence circulating CRP concentrations are associated with late AMD. Design, Setting, and Participants Participants in 2 UK, hospital-based, case-control studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan-European, cross-sectional, population-based study (the European Eye [EUREYE] Study) were recruited between November 6, 2000, and April 30, 2007. Participants underwent dilated stereo-digital fundus photography graded according to the International Classification of Age-related Maculopathy and Macular Degeneration. There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and 192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD cases (n = 574) were included only from the EUREYE Study. Data analysis was performed from August 1 to November 30, 2016. Four common single-nucleotide polymorphisms (rs1205,rs1130864,rs1800947, andrs3093077) were selected based on demonstrated influence on circulating CRP concentrations in the literature. In one study, genotyping ofrs3093077failed, andrs1800947was typed in only 1 study. Main Outcomes and Measures A genetic multiplicative model was used for the association of single-nucleotide polymorphisms with late AMD adjusted for age and sex. Results Among the 1727 patients with late AMD, the mean (SD) age was 78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was 74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3 studies, neitherrs1205(odds ratio [OR], 0.99; 95% CI, 0.86-1.14) norrs1130864(OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic atrophy,rs1205had an OR of 0.91 (95% CI, 0.74-1.13) andrs1130864had an OR of 0.94 (95% CI, 0.76-1.16). For neovascular AMD,rs1205had an OR of 1.01 (95% CI, 0.87-1.19) andrs1130864had an OR of 0.99 (95% CI, 0.84-1.16). There was no association ofrs3093077andrs1800947with late AMD or any late AMD phenotype. There were no significant findings for early AMD. Conclusions and Relevance Our results do not support a causal association between CRP concentrations and AMD.