Figure 2.

Gene expression in peripheral blood mononuclear cells. (A) Heatmap of 973 differentially expressed genes (DEG). Samples and genes (columns and rows, respectively) are reordered on the basis of the normalized expression value and give rise to groups of genes and samples with similar expression levels, according to the color key. The samples (column) were clustered into two groups according to rs4947296: three individuals with CC genotype (risk) and seven individuals with TT genotype (protective). (B) The shortest path from Fn14 (TNFRSF12A) to NFKB genes. DEG in mononuclear cells (adjusted p < 0.001), according to the homozygous genotype, were used to predict involved pathways. The network was retrieved from three MetaCore pathways [“apoptosis and survival Apoptotic tumor necrosis factor (TNF)-family pathways,” “signal transduction NF-κB activation pathways,” and “apoptosis and survival Anti-apoptotic TNFs-NF-κB-Bcl-2 pathway”] enriched in our pathway enrichment analysis. Log fold change is color-coded, where red nodes indicate upregulated genes, whereas blue nodes indicate downregulated genes. Activation interactions are indicated by arrow heads, whereas inhibitory interactions are indicated by blunted heads. Black edges indicate physical binding interaction, purple edges indicate phosphorylation, and brown edges indicate ubiquitination. Genes with thick purple margin are DEG. (C) Quantitative RT-PCR validation of genes involved in the TWEAK/Fn14 pathway (NFKB1, Fn14, BIRC3, FADD, NFKBIE, FOS, APAF1, CASP3, CASP6, CASP9, CYCS, and IKBKG) (*p < 0.03, **p < 0.0005).