Association of neovascular age-related macular degeneration with specific gene expression patterns in peripheral white blood cells.

Purpose: Inflammation probably plays a major role in the pathogenesis of age-related macular degeneration (AMD). The authors evaluated whether AMD is associated with gene expression patterns in white blood cells (WBCs) and whether such a pattern may serve as a biomarker for the disease.

Methods: Microarray analysis of gene expression in peripheral WBCs was performed on patients with neovascular AMD (NVAMD; n = 16) and controls (n = 16). Results were validated using quantitative real-time RT-PCR (QPCR) on another set of patients (n = 14) and controls (n = 16), respectively. QPCR findings were evaluated using receiver operator characteristic (ROC) curves and correlated with genotyping for the major risk single nucleotide polymorphisms (SNPs) for AMD in the genes for complement factor H and LOC387715.

Results: NVAMD-associated expression was identified for eight sequences (false discovery rate [FDR] = 0%) and 167 sequences (FDR = 10%), respectively. There was an enrichment of genes involved in antigen presentation among the AMD-associated genes (P = 0.0029). QPCR confirmed increased expression (1.6- to 4.3-fold) of four genes (HSPA8, IGHG1, ANXA5, VKORC1) in association with NVAMD (P = 0.02-0.0002). Area under the curve for these genes according to ROC analysis ranged from 0.776 to 0.815. Gene expression was not associated with genotyping for risk SNPs or WBC counts.

Conclusions: NVAMD is associated with altered gene expression in peripheral WBCs that is not underlined by the major risk SNPs for the disease. Such altered expression may potentially serve as a biomarker for the disease. These data support the involvement of systemic immune response in the pathogenesis of AMD.