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Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene

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In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp α1/Hp α2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs.

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References

  • LM Brzustowicz JE Hayter KA Hodgkinson EW Chow AS Bassett (2002) ArticleTitleFine mapping of the schizophrenia susceptibility locus on chromosome 1q22 Hum Hered 54 199–209 Occurrence Handle12771552 Occurrence Handle1:CAS:528:DC%2BD3sXktVKntbc%3D Occurrence Handle10.1159/000070665

    Article  PubMed  CAS  Google Scholar 

  • LM Brzustowicz KA Hodgkinson EW Chow WG Honer AS Bassett (2000) ArticleTitleLocation of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22 Science 288 678–682 Occurrence Handle10784452 Occurrence Handle1:CAS:528:DC%2BD3cXivFGgsrw%3D Occurrence Handle10.1126/science.288.5466.678

    Article  PubMed  CAS  Google Scholar 

  • M Diarra-Mehrpour J Bourguignon R Sesboue MG Mattei E Passage JP Salier JP Martin (1989) ArticleTitleHuman plasma inter-alpha-trypsin inhibitor is encoded by four genes on three chromosomes Eur J Biochem 179 147–154 Occurrence Handle2465147 Occurrence Handle1:CAS:528:DyaL1MXntVCisg%3D%3D Occurrence Handle10.1111/j.1432-1033.1989.tb14532.x

    Article  PubMed  CAS  Google Scholar 

  • S Duan Y Xu W Chen Z Liu T Guo J Gao L Bian Y Zhen X Li X Zhang Y Pan N Gu G Feng L He (2004) ArticleTitleNo association between the promoter variants of tumor necrosis factor alpha (TNF-alpha) and schizophrenia in Chinese Han population Neurosci Lett 366 139–143 Occurrence Handle15276234 Occurrence Handle1:CAS:528:DC%2BD2cXmtVSqurY%3D Occurrence Handle10.1016/j.neulet.2004.05.039

    Article  PubMed  CAS  Google Scholar 

  • G Floyd-Smith AS Whitehead HR Colten U Francke (1986) ArticleTitleThe human C-reactive protein gene (CRP) and serum amyloid P component gene (APCS) are located on the proximal long arm of chromosome 1 Immunogenetics 24 171–176 Occurrence Handle3759147 Occurrence Handle1:CAS:528:DyaL2sXht1Ci

    PubMed  CAS  Google Scholar 

  • S Germer MJ Holland R Higuchi (2000) ArticleTitleHigh-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR Genome Res 10 258–266 Occurrence Handle10673283 Occurrence Handle1:CAS:528:DC%2BD3cXhsVOks7k%3D Occurrence Handle10.1101/gr.10.2.258

    Article  PubMed  CAS  Google Scholar 

  • TA Greenwood M Alexander PE Keck S McElroy AD Sadovnick RA Remick JR Kelsoe (2001) ArticleTitleEvidence for linkage disequilibrium between the dopamine transporter and bipolar disorder Am J Med Genet 105 145–151 Occurrence Handle11304827 Occurrence Handle1:STN:280:DC%2BD3MzgslKgtw%3D%3D Occurrence Handle10.1002/1096-8628(2001)9999:9999<::AID-AJMG1161>3.0.CO;2-8

    Article  PubMed  CAS  Google Scholar 

  • C Guha M Osawa PA Werner RM Galbraith GV Paddock (1995) ArticleTitleRegulation of human Gc (vitamin D-binding) protein levels: hormonal and cytokine control of gene expression in vitro Hepatology 21 1675–1681 Occurrence Handle7539397 Occurrence Handle1:CAS:528:DyaK2MXmvVCisLg%3D Occurrence Handle10.1016/0270-9139(95)90474-3

    Article  PubMed  CAS  Google Scholar 

  • R Hashimoto M Yoshida N Ozaki Y Yamanouchi N Iwata T Suzuki T Kitajima M Tatsumi K Kamijima H Kunugi (2004) ArticleTitleAssociation analysis of the −308G > A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia J Neural Transm 111 217–221 Occurrence Handle14767724 Occurrence Handle1:CAS:528:DC%2BD2cXhtVOlsLo%3D Occurrence Handle10.1007/s00702-003-0089-4

    Article  PubMed  CAS  Google Scholar 

  • M Hornig DB Goodman M Kamoun JD Amsterdam (1998) ArticleTitlePositive and negative acute phase proteins in affective subtypes J Affect Disord 49 9–18 Occurrence Handle9574855 Occurrence Handle1:STN:280:DyaK1c3jsVWmsQ%3D%3D Occurrence Handle10.1016/S0165-0327(97)00180-8

    Article  PubMed  CAS  Google Scholar 

  • V Ionasescu T Burns C Searby R Ionasescu (1987) ArticleTitleLinkage between the loci for Duffy (FY) and serum amyloid P component (APCS) on human chromosome 1 Cytogenet Cell Genet 45 240–241 Occurrence Handle3691191 Occurrence Handle1:STN:280:DyaL1c%2FotFOmsA%3D%3D

    PubMed  CAS  Google Scholar 

  • H Katila B Appelberg M Hurme R Rimon (1994) ArticleTitlePlasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders Schizophr Res 12 29–34 Occurrence Handle8018583 Occurrence Handle1:STN:280:DyaK2c3ovFehsg%3D%3D Occurrence Handle10.1016/0920-9964(94)90081-7

    Article  PubMed  CAS  Google Scholar 

  • CA Kaufmann B Suarez D Malaspina J Pepple D Svrakic PD Markel J Meyer CT Zambuto K Schmitt TC Matise JM Harkavy Friedman C Hampe H Lee D Shore D Wynne SV Faraone MT Tsuang CR Cloninger (1998) ArticleTitleNIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees Am J Med Genet 81 282–289 Occurrence Handle9674972 Occurrence Handle1:STN:280:DyaK1czjslOhuw%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(19980710)81:4<282::AID-AJMG2>3.0.CO;2-W

    Article  PubMed  CAS  Google Scholar 

  • KS Kendler (1988) ArticleTitleThe impact of varying diagnostic thresholds on affected sib pair linkage analysis Genet Epidemiol 5 407–419 Occurrence Handle3209053 Occurrence Handle1:STN:280:DyaL1M%2FptF2lsA%3D%3D Occurrence Handle10.1002/gepi.1370050605

    Article  PubMed  CAS  Google Scholar 

  • SS Kety PH Wender B Jacobsen LJ Ingraham L Jansson B Faber DK Kinney (1994) ArticleTitleMental illness in the biological and adoptive relatives of schizophrenic adoptees. Replication of the Copenhagen Study in the rest of Denmark Arch Gen Psychiatry 51 442–455 Occurrence Handle8192547 Occurrence Handle1:STN:280:DyaK2c3ltVWjsQ%3D%3D

    PubMed  CAS  Google Scholar 

  • J Kowalski P Blada K Kucia A Madej ZS Herman (2001) ArticleTitleNeuroleptics normalize increased release of interleukin-1 beta and tumor necrosis factor-alpha from monocytes in schizophrenia Schizophr Res 50 169–175 Occurrence Handle11439237 Occurrence Handle1:STN:280:DC%2BD3MzosFCitg%3D%3D Occurrence Handle10.1016/S0920-9964(00)00156-0

    Article  PubMed  CAS  Google Scholar 

  • MR Langlois JR Delanghe (1996) ArticleTitleBiological and clinical significance of haptoglobin polymorphism in humans Clin Chem 42 1589–1600 Occurrence Handle8855140 Occurrence Handle1:CAS:528:DyaK28Xmt1eqs70%3D

    PubMed  CAS  Google Scholar 

  • A Lin G Kenis S Bignotti GJ Tura R De Jong E Bosmans R Pioli C Altamura S Scharpe M Maes (1998) ArticleTitleThe inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6 Schizophr Res 32 9–15 Occurrence Handle9690329 Occurrence Handle1:STN:280:DyaK1czlsVOrtA%3D%3D Occurrence Handle10.1016/S0920-9964(98)00034-6

    Article  PubMed  CAS  Google Scholar 

  • M Maes E Bosmans J Calabrese R Smith HY Meltzer (1995) ArticleTitleInterleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers J Psychiatry Res 29 141–152 Occurrence Handle1:STN:280:DyaK2MzpsFyjtw%3D%3D Occurrence Handle10.1016/0022-3956(94)00049-W

    Article  CAS  Google Scholar 

  • M Maes J Delange R Ranjan HY Meltzer R Desnyder W Cooremans S Scharpe (1997) ArticleTitleAcute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs Psychiatry Res 66 1–11 Occurrence Handle9061799 Occurrence Handle1:CAS:528:DyaK2sXhvFOkt7s%3D Occurrence Handle10.1016/S0165-1781(96)02915-0

    Article  PubMed  CAS  Google Scholar 

  • M Maes J Delanghe CL Bocchio S Bignotti GB Tura R Pioli R Zanardini CA Altamura (2001) ArticleTitleHaptoglobin polymorphism and schizophrenia: genetic variation on chromosome 16 Psychiatry Res 104 1–9 Occurrence Handle11600184 Occurrence Handle1:CAS:528:DC%2BD3MXntlOqu7k%3D Occurrence Handle10.1016/S0165-1781(01)00298-0

    Article  PubMed  CAS  Google Scholar 

  • M Maziade A Fournier D Phaneuf D Cliche JP Fournier MA Roy C Merette (2002) ArticleTitleChromosome 1q12-q22 linkage results in eastern Quebec families affected by schizophrenia Am J Med Genet 114 51–55 Occurrence Handle11840506 Occurrence Handle10.1002/ajmg.1616

    Article  PubMed  Google Scholar 

  • P McGuffin MJ Owen AE Farmer (1995) ArticleTitleGenetic basis of schizophrenia Lancet 346 678–682 Occurrence Handle7658823 Occurrence Handle1:STN:280:DyaK2MzoslOktw%3D%3D Occurrence Handle10.1016/S0140-6736(95)92285-7

    Article  PubMed  CAS  Google Scholar 

  • EM Meisenzahl D Rujescu A Kirner I Giegling N Kathmann G Leinsinger K Maag U Hegerl K Hahn HJ Moller (2001) ArticleTitleAssociation of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia Am J Psychiatry 158 1316–1319 Occurrence Handle11481169 Occurrence Handle1:STN:280:DC%2BD3MvjtlGgtw%3D%3D Occurrence Handle10.1176/appi.ajp.158.8.1316

    Article  PubMed  CAS  Google Scholar 

  • DM Nielsen MG Ehm BS Weir (1998) ArticleTitleDetecting marker-disease association by testing for Hardy-Weinberg disequilibrium at a marker locus Am J Hum Genet 63 1531–1540 Occurrence Handle9867708 Occurrence Handle1:STN:280:DyaK1M%2FotV2rsg%3D%3D Occurrence Handle10.1086/302114

    Article  PubMed  CAS  Google Scholar 

  • A Pandey M Mann (2000) ArticleTitleProteomics to study genes and genomes Nature 405 837–846 Occurrence Handle10866210 Occurrence Handle1:CAS:528:DC%2BD3cXksV2jt74%3D Occurrence Handle10.1038/35015709

    Article  PubMed  CAS  Google Scholar 

  • M Rothermundt V Arolt TA Bayer (2001) ArticleTitleReview of immunological and immunopathological findings in schizophrenia Brain Behav Immun 15 319–339 Occurrence Handle11782102 Occurrence Handle1:CAS:528:DC%2BD38Xit1ymsA%3D%3D Occurrence Handle10.1006/brbi.2001.0648

    Article  PubMed  CAS  Google Scholar 

  • C Rudduck G Franzen N Frohlander L Lindstrom (1985) ArticleTitleHaptoglobin and transferrin types in schizophrenia Hum Hered 35 65–68 Occurrence Handle3857216 Occurrence Handle1:STN:280:DyaL2M7otFagtw%3D%3D Occurrence Handle10.1159/000153519

    Article  PubMed  CAS  Google Scholar 

  • N Saha Y Liu JS Tay J Basair CH Ho (1992) ArticleTitleAssociation of haptoglobin types with serum lipids and apolipoproteins in a Chinese population Clin Genet 42 57–61 Occurrence Handle1424232 Occurrence Handle1:STN:280:DyaK3s%2FkslChtg%3D%3D Occurrence Handle10.1111/j.1399-0004.1992.tb03140.x

    Article  PubMed  CAS  Google Scholar 

  • PC Sham D Curtis (1995) ArticleTitleMonte Carlo tests for associations between disease and alleles at highly polymorphic loci Ann Hum Genet 59 97–105 Occurrence Handle7762987 Occurrence Handle1:STN:280:DyaK2M3otlansg%3D%3D

    PubMed  CAS  Google Scholar 

  • SH Shaw M Kelly AB Smith G Shields PJ Hopkins J Loftus SH Laval A Vita M De Hert LR Cardon TJ Crow R Sherrington LE DeLisi (1998) ArticleTitleA genome-wide search for schizophrenia susceptibility genes Am J Med Genet 81 364–376 Occurrence Handle9754621 Occurrence Handle1:STN:280:DyaK1cvisFGqsA%3D%3D Occurrence Handle10.1002/(SICI)1096-8628(19980907)81:5<364::AID-AJMG4>3.0.CO;2-T

    Article  PubMed  CAS  Google Scholar 

  • Y Shi X Zhao L Yu R Tao J Tang Y La Y Duan B Gao N Gu Y Xu G Feng S Zhu H Liu H Salter L He (2004) ArticleTitleGenetic structure adds power to detect schizophrenia susceptibility at SLIT3 in the Chinese Han population Genome Res 14 1345–1349 Occurrence Handle15231749 Occurrence Handle1:CAS:528:DC%2BD2cXlvFWjt7c%3D Occurrence Handle10.1101/gr.1758204

    Article  PubMed  CAS  Google Scholar 

  • RN Simmers I Stupans GR Sutherland (1986) ArticleTitleLocalization of the human haptoglobin genes distal to the fragile site at 16q22 using in situ hybridization Cytogenet Cell Genet 41 38–41 Occurrence Handle3455911 Occurrence Handle1:CAS:528:DyaL28Xht1Citr4%3D Occurrence Handle10.1159/000132193

    Article  PubMed  CAS  Google Scholar 

  • O Smithies (1955) ArticleTitleZone electrophoresis in starch gels: group variations in the serum proteins of normal human adults Biochem J 61 629–641 Occurrence Handle13276348 Occurrence Handle1:CAS:528:DyaG28XitVChug%3D%3D

    PubMed  CAS  Google Scholar 

  • O Smithies NF Walker (1956) ArticleTitleNotation for serum-protein groups and the genes controlling their inheritance Nature 178 694–695 Occurrence Handle13369501 Occurrence Handle1:CAS:528:DyaG2sXhtlOrug%3D%3D Occurrence Handle10.1038/178694a0

    Article  PubMed  CAS  Google Scholar 

  • YH Song K Ray SA Liebhaber NE Cooke (1998) ArticleTitleVitamin D-binding protein gene transcription is regulated by the relative abundance of hepatocyte nuclear factors 1alpha and 1beta J Biol Chem 273 28408–28418 Occurrence Handle9774468 Occurrence Handle1:CAS:528:DyaK1cXntVClsLY%3D Occurrence Handle10.1074/jbc.273.43.28408

    Article  PubMed  CAS  Google Scholar 

  • RL Spitzer JB Williams M Gibbon MB First (1992) ArticleTitleThe Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description Arch Gen Psychiatry 49 624–629 Occurrence Handle1637252 Occurrence Handle1:STN:280:DyaK38zksVGjuw%3D%3D

    PubMed  CAS  Google Scholar 

  • JX Tang J Zhou JB Fan XW Li YY Shi NF Gu GY Feng YL Xing JG Shi L He (2003) ArticleTitleFamily-based association study of DTNBP1 in 6p22.3 and schizophrenia Mol Psychiatry 8 717–718 Occurrence Handle12888799 Occurrence Handle1:CAS:528:DC%2BD3sXlvVGjtLs%3D Occurrence Handle10.1038/sj.mp.4001287

    Article  PubMed  CAS  Google Scholar 

  • GK Thaker WT Carpenter SuffixJr (2001) ArticleTitleAdvances in schizophrenia Nat Med 7 667–671 Occurrence Handle11385502 Occurrence Handle1:CAS:528:DC%2BD3MXktlGkurg%3D Occurrence Handle10.1038/89040

    Article  PubMed  CAS  Google Scholar 

  • C Turleau J de Grouchy F Chavin-Colin F Dore J Seger MD Dautzenberg M Arthuis C Jeanson (1984) ArticleTitleTwo patients with interstitial del (14q), one with features of Holt-Oram syndrome. Exclusion mapping of PI (alpha-1-antitrypsin) Ann Genet 27 237–240 Occurrence Handle6335371 Occurrence Handle1:STN:280:DyaL2M7itVKrsg%3D%3D

    PubMed  CAS  Google Scholar 

  • DM Vander Putten EF Torrey AB Larive CR Merril (1996) ArticleTitlePlasma protein variations in monozygotic twins discordant for schizophrenia Biol Psychiatry 40 437–442 Occurrence Handle8879462 Occurrence Handle1:STN:280:DyaK2s%2Fjtlyjtg%3D%3D Occurrence Handle10.1016/0006-3223(95)00467-X

    Article  PubMed  CAS  Google Scholar 

  • EG Welles MK Boudreaux JW Tyler (1993) ArticleTitlePlatelet, antithrombin, and fibrinolytic activities in taurine-deficient and taurine-replete cats Am J Vet Res 54 1235–1243 Occurrence Handle8214889 Occurrence Handle1:CAS:528:DyaK3sXmsVOjsbs%3D

    PubMed  CAS  Google Scholar 

  • CT Wong WF Tsoi N Saha (1996) ArticleTitleAcute phase proteins in male Chinese schizophrenic patients in Singapore Schizophr Res 22 165–171 Occurrence Handle8958601 Occurrence Handle1:STN:280:DyaK2s7hslGltg%3D%3D Occurrence Handle10.1016/S0920-9964(96)00037-0

    Article  PubMed  CAS  Google Scholar 

  • S Ye S Dhillon X Ke AR Collins IN Day (2001) ArticleTitleAn efficient procedure for genotyping single nucleotide polymorphisms Nucleic Acids Res 29 E88 Occurrence Handle11522844 Occurrence Handle1:STN:280:DC%2BD3MvnvFCltw%3D%3D Occurrence Handle10.1093/nar/29.17.e88

    Article  PubMed  CAS  Google Scholar 

  • XY Zhang DF Zhou PY Zhang GY Wu LY Cao YC Shen (2002) ArticleTitleElevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology Schizophr Res 57 247–258 Occurrence Handle12223256 Occurrence Handle10.1016/S0920-9964(01)00296-1

    Article  PubMed  Google Scholar 

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Wan, C., La, Y., Zhu, H. et al. Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids 32, 101–108 (2007). https://doi.org/10.1007/s00726-005-0292-8

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