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R. Blanco, W. Fung; Molecular Classification of Age Related Macular Degeneration by Gene Expression Profiling. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4628.
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to explore the hypothesis that gene expression profiling of peripheral blood mononuclear cells (PBMCs) may provide new insights into the pathophysiology of age related macular degeneration (ARMD) and identify genetic biomarker (s) for individuals who may be at risk for developing advanced ARMD.
10 patients with bilateral "wet" ARMD, according to the classification of the International ARMD group and 10 control subjects were selected. We isolated the total messenger RNA from PBMCs samples, prepared fluorescent complementary DNA from the messenger RNA and hybridized them to microarrays containing probes from 54.000 cDNA (Affymetrix Human U133 plus 2.0) obtaining quantitative and comparative measurements for each gene. Linear models were fitted for each gene on (i) ARMD status only, (ii) Sex only, and (iii) ARMD+Sex simultaneously to derive sex-adjusted ARMD effect using the limma package (Smyth G. 2004) in R/Bioconductor. Moderated t-statistics & the associated p-values were calculated, as well as B-statistics, the log posterior odds ratio that a gene is DE versus not DE.
In this study, no genes passed our statistical criteria with multiple testing consideration, such as Bonferroni-adjust p-value, FDR or B>0. The heatmap showed that gender effects dominated the gene variability among samples. 154 genes were seen to have a >1.5x change (M>0.58 or M<-0.58), like the MGST1 (microsomal glutathion-S-transferase), mainly involved in oxidative stress processes.
Unraveling the temporal relationships between the multiple inflammatory subsystems involved in drusen biogenesis in larger samples may help us identify a panel of molecular markers.
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