Abstract
Purpose: :
Impaired inhibition of the alternative complement pathway by complement factor H (CFH) is linked to AMD based on the strong association between CFH Y402H and AMD. Chlamydia pneumoniae (C. pneumoniae) infection is known to trigger the alternative pathway and thus may be implicated in AMD pathogenesis. To date, data of the association between C. pneumonia and AMD are limited, with small sample sizes and controversial results. We investigated if C. pneumoniae infection is associated with AMD and if there is any relationship between C. pneumonia, CFH variants, and risk of AMD.
Methods: :
Genomic DNA extracted from peripheral blood of 148 advanced AMD patients and 162 age-matched controls from the NEI cohort was subjected to CFH intron G/C (rs380390) SNPs using Taqman and PCR-RFLP, and PCR amplification of 16S rRNA gene of C. pneumoniae. Genomic DNA was also collected, following microdissection of macular cells from archived ocular slides, from 59 AMD and 16 age-matched non-AMD subjects. Chi-square testing was performed for case-control analysis.
Results: :
PCR signals for 16S rRNA gene of C. pneumoniae were present in blood specimens of 30/148 (20.3%) AMD patients and 17/162 (10.5%) age-matched controls, with a statistical significance (p<0.017) between C. pneumonia infection and risk of AMD. CFH C/C was significantly associated with AMD (p<0.001). The distribution of CFH variant are 12/51 (23.5%) in G/G, 9/53 (17.0%) in G/C and 9/44 (20.5%) in C/C in AMD patients and 3/76 (4%), 11/70 (15.7%) and 3/16 (18.8%) in controls, respectively. CFH genotype did not affect AMD risk in patients with C. pneumonia infection, and conversely, presence of C. pneumonia infection did not affect AMD risk in those with risk-conferring CFH genotypes. The C. pneumonia DNA was also seen in archived specimens of 2/59 AMD and 1/16 non-AMD patients.
Conclusions: :
We demonstrated higher percentage infection of C. pneumoniae in AMD than in non-AMD patients, suggesting a possible association between AMD and C. pneumoniae infection. The pathogenesis may involve circulating C. pneumonia elementary bodies and/or C. pneumoniae reticulate bodies in macrophage and other cells to AMD lesion. C. pneumonia may be one of possible infective triggers for AMD. Our data suggest that CFH may not be involved in the pathogenesis of C. pneumoniae-associated AMD. The role of C. pneumoniae in AMD needs further study.
Keywords: microbial pathogenesis: clinical studies • age-related macular degeneration • pathology techniques