Table 3.
Examples of functional involvement of blood transcriptional abnormalities in AD
| Gene functions | Genes altered (≥2fold, FDR≤1%) |
|---|---|
| Neurological functions | CNR1, NRGN, SYNGR1, CPNE6, GABRB1, GRIN3A, GABRP, SLC6A4, NES, SLC6A9, SLC6A5, GAN, NAV3, DBI, CRBN, CNTNAP1, PCP4, OPRL1, NEGR1, NCAM2, CRLF1, DOCK7, INA, MOG, CNP, MAG, GMFB |
| Brain-specific/enriched | HAPLN2, PVALB, CPNE6, GABRB1, CALY, MAG, SV2A, ATP6V1G2, KCNQ3, NKX1-2, CPLX2, TMEM145, INA, *SNCB |
| Somatic-specific/enriched | AHSG, SERPINA6, UMOD, MYL4, VIL1, CASQ1, TNNI1, CLPS, CELA2B, CPB1, *HR, DIO2, LALBA |
| Diabetes-linked | ICA1, GAL, IGF1, CASP3, ADRB2, CLU, PTPN22, ADIPOR1 |
| Inflammation | CD4, CD28, CD3G, IL17F, CTLA4, ITK, LTA, GZMA, GNLY, IL15, LST1, *CD70, CD69, CXCR4, TIA1, CCR2, CCR3, CCR4, CXCR4, CD80, *CD24, IL7, CSF1, MSR1, #HLA-DQA2, CXCL16, IFNG, IL37, CD226, GZMA, GNLY, KLRF1, KIR2DL4, C9, C2, C4B, CFH, CR1, C5AR2, CD46, IRAK1, MAP3K8, SIKE, UNC93B1, CHUK, CD36, CTSE, LTA, TNFAIP8, TNFSF8, C1QTNF5, TNFRSF14, FAS, TAB2, TAB3, MAPK3, MAPK6, MAPK8, MAPK9, MAP2K3, MAP3K2, MAP3K7, MAP3K8, MAP3K11, MAP4K5, TGFB1I1, NKIRAS2, NKIRAS2, NKAPL, NKRF, IKBKB, CHUK, SIKE, ICA1, SSB, TINAGL1, PNMA5, BST2, FCN3, SP100, SLC25A16, COL4A3BP |
| Cytoskeletal | MAG, MOG, TAGLN, CLDN10, MACF1, PRNP |
| Extracellular matrix components | HSPG2, HYAL3, HAPLN2, AHSG, CSPG4, GPC4, CHI3L1, LRG1, GP1BB, TNXB, SV2A, SV2C, LAMA3, LAMB1, LAMB2, LAMC3, ELN, EMILIN3, COL4A4, COL7A1, COL11A2, COL19A1, COL27A1, AGRN, MMP9, MMP19, ADAM11, ADAM21, *ADAM22, ADAM33, PLAU, CLU |
| Ion Channels | SLC5A6, SLC5A2, SLC17A4, SLC5A3, SLC4A7, SLC8A1, SLC24A3, SCNN1D,, SLC9A7, CAMK2D, CACNG8, CACNG6, SLC24A3, CASK, KCNA3, *KCNAB2, KCNQ3, KCNC3, KCND3, KCTD12, KCNH2, KCNH8, KCNK15, KCNK16, KCNK7, KCNQ2 |
| Oxidative stress/redox | CMC1, CA5B, SLC25A24, SLC25A16, UCP3, TOMM7, MTCH1, DIABLO, MCAT, ATP5I, FIS1, GPD2, ABCD4, ABCB10, SMOX, CYP2F1, CYP2R1, CYP1B1, CYP2B6, CYP20A1, CYP4F2, CYP4F30P, CYP21A2, CYP4V2, GPX1, GPX4, GPX5, GPX2, OXR1, PON2, PRDX6, PRDX2, CYGB, PSIP1, TXNRD1, BLVRB, NAPRT1, COX6C, COX6B2, COX11, COX7A2L, COX7C, COX7B, COX16, COX17, ALDH3B1, NDUFS4, *MDH1, ADH5 |
| DNA damage/repair | ATM, ATR, BRCC3, CHEK2, MDC1, MRE11A, XRCC4, TONSL, RRM2B, ERCC2, XPA, DCLRE1A, SFR1 |
| Apoptosis/cell death | ATK1, CASP3, CASP8, MAPK3, MAPK9, FAS, KIR2DL4, PDCD7, CCNL2, SIAH2 SIAH1 |
| Cell survival/repair | SMNDC1, CCAR1, DDX3X, PRKAA1, MST4 |
| Oncogenes | KRAS, NRAS, WNT4, MYCNOS, BCL2, BCL11A |
| Tumor suppressor genes | RB1, OSM, TP53INP1, TP53RK, APC, TNK1, RERG, RRAS2, BNIP3L, BAG6 |
Total RNA from peripheral blood of AD patients (n=9) and healthy controls (n=10) were assayed by genome-wide gene expression microarrays. Functional analyses of array data were performed using IPA and GeneCards database Listed are examples of major functional involvement of dysregulated genes in the blood of AD patients. Underlined: known autoantigens. Unless indicated, all AD blood genes were altered ≥2 fold, FDR≤1%.
*
: Genes altered ≥2 fold, FDR≤2%.
#
: Genes altered ≥2 fold, FDR≤8%.