Association of Neovascular Age-Related Macular Degeneration with Specific Gene Expression Patterns in Peripheral White Blood Cells

黄斑变性 外周血 白色(突变) 外围设备 医学 病理 眼科 基因 生物 遗传学 免疫学 内科学
作者
Michal Lederman,Avraham Weiss,Itay Chowers
出处
期刊:Investigative Ophthalmology & Visual Science [Association for Research in Vision and Ophthalmology (ARVO)]
卷期号:51 (1): 53-53 被引量:30
标识
DOI:10.1167/iovs.08-3019
摘要

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.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.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.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.
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