Biomarkers for diagnosis of transient ischemic attacks

Abstract

The present invention provides methods and compositions for diagnosing and predicting the risk and cause of transient ischemic attacks (TIA).

1 . A method for diagnosing a transient ischemic attack (TIA) or a predisposition for experiencing TIA, the method comprising: determining a level of expression of a plurality of TIA-associated biomarkers in a biological sample from a patient, wherein an increase or decrease of the level of expression compared to a control indicates that the patient has suffered or is at risk of experiencing TIA, wherein the plurality of TIA-associated biomarkers is selected from the biomarkers set forth in Tables 1, 2, 5A, 5B, 5C, 5D, 7, 8 and 9. 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein an increased expression level of one or more TIA-associated biomarkers selected from the group consisting of DKFZP434B061, FAM55D, F1130375, IGFBP5, LTBR and SCN2A indicates that the patient has suffered or is at risk of experiencing TIA. 
     
     
         7 . The method of  claim 1 , wherein an increased expression level of one or more TIA-associated biomarkers selected from the group consisting of GABRB2, ELAVL3, TWIST1, DPPA4, DKFZP434P211, DLX6, ZNF479, ASTN2, SNX31, ALS2CR11, LOC440345 indicates that the patient has suffered or is at risk of experiencing TIA. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein a decreased expression level of one or more TIA-associated biomarkers selected from the group consisting of ATG9B, DIP2C, EDAR, GSTM1, GUSBL2, SMURF2, ZNF512B indicates that the patient has suffered or is at risk of experiencing TIA. 
     
     
         10 . The method of  claim 1 , wherein a decreased expression level of one or more TIA-associated biomarkers selected from the group consisting of NBPF10///RP11-9412.2, SFXN1, SPIN3, UNC84A, OLFM2, PPM1K, P2RY10, ZNF512B, MORF4L2, GIGYF2, ERAP2, SLFN13, LOC401431, MED6, BAIAP2L1///LOC100128461, LNPEP, MBNL1, NOS3, MCF2L, KIAA1659, SCAMPS, LOC648921, ANAPC5, SPON1, FUS, GPR22, GAL3ST4, METTL3, LOC100131096, FAAH2, SMURF2, SNRPN, FBLN7, GLS, G3BP1, RCAN3, EPHX2, DIP2C, CCDC141, CLTC, FOSB, CACNA1I, UNQ6228, ATG9B, AK5, SPIN3, RBM14, SNRPN, MAN1C1, HELLS, EDAR, SLC3A1, ZNF519, LOC100130070///LOC100130775///LOC100131787///LOC100131905///LOC100132291///LOC100132488///RPS27, ZC3H12B, IQGAP2, SOX8, WHDC1L2, TNPO1, TNFRSF21, TSHZ2, DMRTC1///DMRTC1B, GSTM1, GSTM2, PNMA6A, CAND1, CCND3, GSTM1, GUSBL2 indicates that the patient has suffered or is at risk of experiencing TIA. 
     
     
         11 - 32 . (canceled) 
     
     
         33 . The method of  claim 1 , wherein the level of expression of the biomarker is determined at the transcriptional level. 
     
     
         34 . The method of  claim 1 , wherein the level of expression is determined by detecting hybridization of a TIA-associated gene probe to gene transcripts of the biomarkers in the biological sample. 
     
     
         35 . The method of  claim 34 , wherein the hybridization step is performed on a nucleic acid microarray chip. 
     
     
         36 . The method of  claim 34 , wherein the hybridization step is performed in a microfluidics assay plate. 
     
     
         37 . The method of  claim 1 , wherein the level of expression is determined by amplification of gene transcripts of the biomarkers. 
     
     
         38 . The method of  claim 37 , wherein the amplification reaction is a polymerase chain reaction (PCR). 
     
     
         39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the level of expression of at least 15 biomarkers is determined. 
     
     
         41 . The method of  claim 1 , further comprising the step of obtaining a biological sample. 
     
     
         42 . The method of  claim 1 , wherein the biological sample is blood, serum or plasma. 
     
     
         43 . The method of  claim 1 , wherein the control is the expression level of a plurality of stably expressed endogenous reference biomarkers. 
     
     
         44 . The method of  claim 43 , wherein the one or more endogenous reference biomarkers is selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4 KB, CRTC1, HADHA, MAP1LC3B, KAT5, CDC2L1///CDC2L2, GTSE1, CDC2L1///CDC2L2, TCF25, CHP, LRRC40, hCG 2003956///LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHC5, C9orf23, LRRC45, NACC1, LOC100133445///LOCI-15110 and PEX16 
     
     
         45 . The method of  claim 1 , wherein the control is the expression level of the same biomarker in a healthy individual. 
     
     
         46 . The method of  claim 1 , wherein the control is a threshold level of expression representative of a population of healthy individuals. 
     
     
         47 . The method of  claim 1 , further comprising the step of providing an appropriate treatment or prevention regime for TIA to the patient. 
     
     
         48 . A solid support comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 2, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5A, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5B, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5C, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 5D, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 7, a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 8 and a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 9. 
     
     
         49 . The solid support of  claim 48 , comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of GUSBL2, GSTM1, F1130375, SCN2A, DKFZP434B061, EDAR, ATG9B, DIP2C, LTBR, SMURF2, FAM55D, IGFBP5, and ZNF512B. 
     
     
         50 - 60 . (canceled) 
     
     
         61 . The solid support of  claim 48 , wherein the solid support is a microarray.