title: Identification of differentially expressed genes in blood cells of narcolepsy patients.
abstract: OBJECTIVE
  A close association between the human leukocyte antigen (HLA)-DRB1*1501/DQB1*0602 and abnormalities in some inflammatory cytokines have been demonstrated in narcolepsy. Specific alterations in the immune system have been suggested to occur in this disorder. We attempted to identify alterations in gene expression underlying the abnormalities in the blood cells of narcoleptic patients.
  
  
  METHODS
  Total RNA from 12 narcolepsy-cataplexy patients and from 12 age- and sex-matched healthy controls were pooled. The pooled samples were initially screened for candidate genes for narcolepsy by differential display analysis using annealing control primers (ACP). The second screening of the samples was carried out by semiquantitative PCR using gene-specific primers. Finally, the expression levels of the candidate genes were further confirmed by quantitative real-time PCR using a new set of samples (20 narcolepsy-cataplexy patients and 20 healthy controls).
  
  
  RESULTS
  The second screening revealed differential expression of 4 candidate genes. Among them, MX2 was confirmed as a significantly down-regulated gene in the white blood cells of narcoleptic patients by quantitative real-time PCR.
  
  
  CONCLUSIONS
  We found the MX2 gene to be significantly less expressed in comparison with normal subjects in the white blood cells of narcoleptic patients. This gene is relevant to the immune system. Although differential display analysis using ACP technology has a limitation in that it does not help in determining the functional mechanism underlying sleep/wakefulness dysregulation, it is useful for identifying novel genetic factors related to narcolepsy, such as HLA molecules. Further studies are required to explore the functional relationship between the MX2 gene and narcolepsy pathophysiology.
authors: The Sleep Disorders Project, Department of Sleep Disorders Research, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan. stanaka@prit.go.jp
authors: Susumu
authors: S
authors: Tanaka
authors: Yutaka
authors: Y
authors: Honda
authors: Makoto
authors: M
authors: Honda
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002385:Cataplexy / Q000235:genetics* / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D064547:Myxovirus Resistance Proteins; D009290:Narcolepsy / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; C468762:IFI6 protein, human; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D064547:Myxovirus Resistance Proteins; C115374:PRPF8 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D001613:beta 2-Microglobulin; C462522:ATP6V1E2 protein, human; D019204:GTP-Binding Proteins; D025262:Vacuolar Proton-Translocating ATPases
references: Am J Hum Genet. 2006 Aug;79(2):252-63
references: 16826516
references: Gene. 2001 Jan 10;262(1-2):123-8
references: 11179675
references: Sleep. 2006 May;29(5):601-2
references: 16774147
references: J Exp Biol. 2006 Feb;209(Pt 4):577-89
references: 16449553
references: Neuroimmunomodulation. 2005;12(3):131-40
references: 15905620
references: Ann Neurol. 2004 Dec;56(6):905-8
references: 15562415
references: Tissue Antigens. 1999 Aug;54(2):138-45
references: 10488740
references: RNA. 1999 Jul;5(7):893-908
references: 10411133
references: J Interferon Cytokine Res. 1999 Apr;19(4):309-18
references: 10334381
references: J Virol. 1999 Jun;73(6):4925-30
references: 10233954
references: J Biol Chem. 1997 Dec 19;272(51):32353-9
references: 9405443
references: J Interferon Res. 1990 Dec;10(6):627-36
references: 1964950
references: Adv Virus Res. 1990;38:147-200
references: 1699395
references: Cytogenet Cell Genet. 1990;53(2-3):166-8
references: 1695131
references: Eur J Biochem. 1989 Oct 1;184(3):503-9
references: 2478362
references: EMBO J. 1986 Jul;5(7):1601-6
references: 3017706
references: Cell. 1984 Oct;38(3):745-55
references: 6548414
references: Ann Neurol. 2004 Sep;56(3):382-8
references: 15349865
references: Nat Genet. 2004 Aug;36(8):801-8
references: 15284851
references: Brain Behav Immun. 2004 Jul;18(4):326-32
references: 15157949
references: Nat Genet. 2004 Apr;36(4):361-9
references: 15004559
references: Biochim Biophys Acta. 2003 Jul 11;1614(1):3-13
references: 12873761
references: Hepatology. 2003 May;37(5):1180-8
references: 12717400
references: Traffic. 2002 Oct;3(10):710-7
references: 12230469
references: Genome Res. 2002 Apr;12(4):595-601
references: 11932243
references: Hum Mol Genet. 2001 Jul 15;10(15):1555-62
references: 11468273
references: Arch Intern Med. 2006 Sep 18;166(16):1739-43
references: 16983052
references: Tissue Antigens. 2000 Nov;56(5):446-8
references: 11144293
references: Sleep. 2006 Aug;29(8):1017-24
references: 16944669