Biomarkers for diagnosis of transient ischemic attacks

Patent metadata

Field	Value
Publication number	US-2016237501-A1
Application number	US-201615043577-A
Country	US
Kind code	A1
Filing date	Feb 14, 2016
Priority date	Jul 14, 2010
Publication date	Aug 18, 2016
Grant date	—

Abstract

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

First claim

1 - 47 . (canceled)

48 . A solid support comprising a plurality of nucleic acids that hybridize to a plurality of genes comprising ATG9B, DIP2C, DKFZP434B061, EDAR, FAM55D, FLJ30375, GSTM1, GUSBL2, IGFBP5, LTBR, SCN2A, SMURF2, ZNF512B, wherein genes which are overexpressed or underexpressed less than 1.5-fold in subjects having or suspected of having TIA, in comparison to a control level of expression are excluded.

49 . (canceled)

50 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of SNIP, BXDC5, FAT3, LECT2, THSD4, CCDC144C///LOC100134159, OVOL2, SPTLC3, CLEC4E, GLYATL1, RBMS3, SPIB, DKFZP434L187, GADL1, SHOX, TBX5, UNC5B, PGM5, TIMP2, ELL2, CXADR, and RNF141.

51 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of RPL22, SNIP, SH3GL3, MCTP1, FAT3, SPTLC3, RBMS3, SNRPN, and TIMP2.

52 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of FGD4, F5, ABCA1, LOC100290882, LTB4R, UBXN2B, CKLF, CLEC4E, PHTF1, ENTPD1, OSBPL1A, RRAGD, CPEB2, CKLF, BST1, and CKLF.

53 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of ZNF608, FCHO2, ST3GAL6, ABCA1, THBD, AMN1, QKI, KIAA0319, MCTP1, VNN3, UBR5, FAR2, RBM25, CHMP1B, LAMP2, VAPA, IFRD1, HNRNPH2, REM2, and GAB1.

54 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of THSD4, SNRPN, ASTN2, SNIP, FAT3, TIMM8A, CCDC144C///LOC100134159, ANKRD28, TBX5, PGM5, SCD5, FCRL4, SHOX, CCRL1, LECT2, PTPRD, CCDC144A, LDB3, LOC729222///PPFIBP1, RBMS3, P704P, GYPA, PRTG, GABRB2, HNRNPUL2, ELAVL2, SPTLC3, FOXA2, DLX6, ALDOAP2, and FLJ35934.

55 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of RPL22, LOC100129488, LOC283027, LOC344595, THSD4, FAT3, and P704P.

56 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of SNIP, BXDC5, FAT3, LECT2, THSD4, CCDC144C///LOC100134159, OVOL2, SPTLC3, CLEC4E, GLYATL1, RBMS3, SPIB, DKFZP434L187, GADL1, SHOX, TBX5, UNC5B, PGM5, TIMP2, ELL2, CXADR, RNF141, RPL22, SH3GL3, MCTP1, SNRPN, FGD4, F5, ABCA1, LOC100290882, LTB4R, UBXN2B, CKLF, PHTF1, ENTPD1, OSBPL1A, RRAGD, CPEB2, CKLF, BST1, ZNF608, FCHO2, ST3GAL6, THBD, AMN1, QKI, KIAA0319, MCTP1, VNN3, UBR5, FAR2, RBM25, CHMP1B, LAMP2, VAPA, IFRD1, HNRNPH2, REM2, GAB1, ASTN2, TIMM8A, CCDC144C///LOC100134159, ANKRD28, SCD5, FCRL4, CCRL1, LECT2, PTPRD, CCDC144A, LDB3, LOC729222///PPFIBP1, P704P, GYPA, PRTG, GABRB2, HNRNPUL2, ELAVL2, FOXA2, DLX6, ALDOAP2, FLJ35934, LOC100129488, LOC283027, and LOC344595.

57 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of EBF1, GRM5, TSKS, ENPP2, AP3S2, LRRC37A3, C16orf68, LOC284751, IRF6, LHFP, BANK1, ARHGEF5, ZNF254, TFDP1, COL13A1, GSTK1, ADAMTSL4, P2RX5, LHFP, PIK3C2B, CHURC1, EXT2, HLA-DOA, OOEP, ZNF185, TMEM19, FCRL1, FLJ40125, ARHGEF12, CLEC18A, CD46, PTPN20A///PTPN20B, and C19orf28.

58 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of EBF1, FLJ31945, C16orf68, SLC20A1, DOPEY2, COL13A1, LHFP, LOC284751, GRM5, LOC100144603, MTBP, SHOX2, ARHGEF5, RNF7, CLASP2, GIPC2, RANBP10, CMBL, LOC100127980, CYTH3, PROCR, LOC146880, SLC6A19, ICAM4, C12orf42, ARHGEF12, PRSS35, NT5E, LOC100271832, LHFP, NT5E and AKR1C3.

59 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of CMTM1, COL13A1, SDC4, C6orf164, GPR176, BRUNOL6, SNORA68, MIF///SLC2A11, DUSP16, HIPK2, TTC7A, PPIE, GRLF1, MAP3K7IP1, LOC100129034, PER3, SMC1A, and LRRC43.

60 . The solid support of claim 48 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4KB, CRTC1, HADHA, MAP1LC3B, KAT5, CDC2L1///CDC2L2, GTSE1, 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///LOC115110, PEX16.

61 . The solid support of claim 48 , wherein the solid support is a microarray.

62 . The solid support of claim 48 , wherein genes that are overexpressed or underexpressed less than 1.2-fold in subjects with ischemic stroke, including cardioembolic stroke, atherothrombotic stroke, and stroke subsequent to atrial fibrillation, in comparison to a control level of expression are excluded.

63 . The solid support of claim 48 , wherein the solid support comprises 100 or fewer nucleic acids.

64 . The solid support of claim 48 , further comprising a plurality of nucleic acids comprising Affymetrix probeset ID numbers 1557580_at, 1559695_a_at, 1561767_at, 1563026_at, 1563568_at, 1568589_at, 1568781_at, 216406_at, 229654_at, 231040_at, 231069_at, 231546_at, 233306_at, 236571_at, 237597_at, 237953_at, 242495_at, 242564_at, 242710_at, 244226_s_at, and 244665_at.

65 . A solid support comprising a plurality of nucleic acids that hybridize to a plurality of genes comprising only ATG9B, DIP2C, DKFZP434B061, EDAR, FAM55D, FLJ30375, GSTM1, GUSBL2, IGFBP5, LTBR, SCN2A, SMURF2, ZNF512B, SNIP, BXDC5, FAT3, LECT2, THSD4, CCDC144C///LOC100134159, OVOL2, SPTLC3, CLEC4E, GLYATL1, RBMS3, SPIB, DKFZP434L187, GADL1, SHOX, TBX5, UNC5B, PGM5, TIMP2, ELL2, CXADR, RNF141, RPL22, SH3GL3, MCTP1, FAT3, SPTLC3, RBMS3, SNRPN, FGD4, F5, ABCA1, LOC100290882, LTB4R, UBXN2B, CLEC4E, PHTF1, ENTPD1, OSBPL1A, RRAGD, CPEB2, CKLF, BST1, ZNF608, FCHO2, ST3GAL6, ABCA1, THBD, AMN1, QKI, KIAA0319, MCTP1, VNN3, UBR5, FAR2, RBM25, CHMP1B, LAMP2, VAPA, IFRD1, HNRNPH2, REM2, GAB1, THSD4, SNRPN, ASTN2, FAT3, TIMM8A, CCDC144C///LOC100134159, ANKRD28, TBX5, PGM5, SCD5, FCRL4, SHOX, CCRL1, LECT2, PTPRD, CCDC144A, LDB3, LOC729222///PPFIBP1, RBMS3, P704P, GYPA, PRTG, GABRB2, HNRNPUL2, ELAVL2, SPTLC3, FOXA2, DLX6, ALDOAP2, FLJ35934, RPL22, LOC100129488, LOC283027, LOC344595, THSD4, FAT3, P704P, BXDC5, FAT3, LECT2, THSD4, CCDC144C///LOC100134159, OVOL2, SPTLC3, CLEC4E, GLYATL1, RBMS3, SPIB, DKFZP434L187, GADL1, SHOX, TBX5, UNC5B, PGM5, TIMP2, ELL2, CXADR, RNF141, RPL22, SH3GL3, MCTP1, SNRPN, FGD4, F5, ABCA1, LOC100290882, LTB4R, UBXN2B, PHTF1, ENTPD1, OSBPL1A, RRAGD, CPEB2, BST1, ZNF608, FCHO2, ST3GAL6, THBD, AMN1, QKI, KIAA0319, MCTP1, VNN3, UBR5, FAR2, RBM25, CHMP1B, LAMP2, VAPA, IFRD1, HNRNPH2, REM2, GAB1, ASTN2, TIMM8A, CCDC144C///LOC100134159, ANKRD28, SCD5, FCRL4, CCRL1, LECT2, PTPRD, CCDC144A, LDB3, LOC729222///PPFIBP1, P704P, GYPA, PRTG, HNRNPUL2, FOXA2, DLX6, ALDOAP2, FLJ35934, LOC100129488, LOC283027, LOC344595, EBF1, GRM5, TSKS, ENPP2, AP3S2, LRRC37A3, C16orf68, LOC284751, IRF6, LHFP, BANK1, ARHGEF5, ZNF254, TFDP1, COL13A1, GSTK1, ADAMTSL4, P2RX5, LHFP, PIK3C2B, CHURC1, EXT2, HLA-DOA, OOEP, ZNF185, TMEM19, FCRL1, FLJ40125, ARHGEF12, CLEC18A, CD46, PTPN20A///PTPN20B, C19orf28, EBF1, FLJ

Assignees

• Univ California

Inventors

• Sharp Frank
• Zhan Xinhua
• Jickling Glen C
• Johnston S Claiborne

Classifications

• A61K31/37

  Coumarins, e.g. psoralen · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• G01N2800/2871

  Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event · CPC title

• A61K31/616

  by carboxylic acids, e.g. acetylsalicylic acid · CPC title