Association of neovascular age-related macular degeneration with specific gene expression patterns in peripheral white blood cells.
OBJECTIVE
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.
Lederman
Michal
M
Department of Ophthalmology, Hadassah-Hebrew University Medical Center and The Hebrew University School of Medicine, Jerusalem, Israel.
Weiss
Avraham
A
Chowers
Itay
I
D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D020256:Choroidal Neovascularization / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008268:Macular Degeneration / Q000235:genetics*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064417:Vitamin K Epoxide Reductases
C514392:ARMS2 protein, human; D017304:Annexin A5; D015415:Biomarkers; C493495:CFH protein, human; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D011506:Proteins; D012333:RNA, Messenger; C029702:prolactin-binding protein; D017242:Complement Factor H; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases