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The CLDN5 locus may be involved in the vulnerability to schizophrenia

Published online by Cambridge University Press:  16 April 2020

Z.-Y. Sun
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
J. Wei*
Affiliation:
Schizophrenia Association of Great Britain, Institute of Biological Psychiatry, Bryn Hyfryd, The Crescent, Bangor, Gwynedd LL57 2AG, UK
L. Xie
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
Y. Shen
Affiliation:
The National Center for Genome Research (Beijing), Beijing 100176, China
S.-Z. Liu
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
G.-Z. Ju
Affiliation:
The National Center for Genome Research (Beijing), Beijing 100176, China
J.-P. Shi
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
Y.-Q. Yu
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
X. Zhang
Affiliation:
Jilin University Research Center for Genomic Medicine, School of Public Health, Jilin University, Changchun130021, China
Q. Xu*
Affiliation:
The National Center for Genome Research (Beijing), Beijing 100176, China
G.P. Hemmings
Affiliation:
Schizophrenia Association of Great Britain, Institute of Biological Psychiatry, Bryn Hyfryd, The Crescent, Bangor, Gwynedd LL57 2AG, UK
*
*Corresponding authors. Email address: jwei@sagb.co.uk (J.Wei); xuqi@pumc.edu.cn (Q. Xu).
*Corresponding authors. Email address: jwei@sagb.co.uk (J.Wei); xuqi@pumc.edu.cn (Q. Xu).
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Abstract

The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.

Type
Original article
Copyright
Copyright © 2004 European Psychiatric Association

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References

Bassett, ASChow, EWC. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol Psychiatr 1999;46:882–91.CrossRefGoogle ScholarPubMed
Coon, HJensen, SHolik, JHoff, M, Myles-Worsley, MReimherr, F, et al. Genomic scan for genes predisposing to schizophrenia. Am J Med Genet 1994;54:59–71.CrossRefGoogle Scholar
De Luca, APasini, AAmati, FBotta, ASpalletta, GAlimenti, S, et al. Association study of promoter polymorphism of UFD1L gene with schizophrenia. Am J Med Genet 2001;105:529–33.CrossRefGoogle ScholarPubMed
De Santis, AAddolorato, GRomito, ACaputo, SGiordano, AGambassi, G, et al. Schizophrenic systems and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. J Intern Med 1997;242:421–3.CrossRefGoogle Scholar
Dohan, FCHarper, EHClark, MHRodrigue, RBZigas, V. Is schizophrenia rare if grain is rare? Biol Psychiatr 1984;19:385–99.Google ScholarPubMed
Egan, MFGoldberg, TEKolachana, BSCallicott, JHMazzanti, CMStraub, RE, et al. Effect of COMT Val108/158Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001;98:6917–22.CrossRefGoogle Scholar
Fanning, ASMitic, LLAnderson, JM. Transmembrane protein in the tight junction barrier. J Am Soc Nephrol 1999;10:1337–45.Google ScholarPubMed
Furuse, MFujita, KHiiragi, TFujimoto, KTsukita, S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1988;141:1539–50.CrossRefGoogle Scholar
Furuse, MHata, MFuruse, KYoshida, YHaratake, ASugitani, Y, et al. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 2002;156:1099–111.Google ScholarPubMed
Glatt, SJFaraone, SVTsuang, MT. Association between a functional catechol-O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatr 2003;160:469–76.CrossRefGoogle ScholarPubMed
Gothelf, DFrisch, AMunitz, HRockah, RLaufer, NMozes, T, et al. Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome. Schizophr Res 1999;35:105–12.CrossRefGoogle ScholarPubMed
Jacquet, HRaux, GThibaut, FHecketsweiler, BHouy, EDemilly, C, et al. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet 2002;11:2243–9.CrossRefGoogle Scholar
Karayiorgou, MMorris, MAMorrow, BShprintzen, RJGoldberg, RBorrow, J, et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci USA 1995;92:7612–6.CrossRefGoogle ScholarPubMed
Kremer, IPinto, MMurad, IMuhaheed, MBannoura, IMuller, DJ, et al. Family-based and case-control study of catechol-O-methyltransferase in schizophrenia among Palestinian Arabs. Am J Med Genet 2003;119B:35–9.CrossRefGoogle ScholarPubMed
Li, TBall, DZhao, JMurray, RMLiu, XSham, PC, et al. Family-based linkage locus disequilibrium mapping using SNP marker haplotypes: application to a potential for schizophrenia at chromosome 22q11. Mol Psychiatr 2000;5:77–8.CrossRefGoogle ScholarPubMed
Li, TSham, PCVallada, HXie, TTang, XMurray, RM, et al. Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatr Genet 1996;6:131–3.CrossRefGoogle Scholar
Liebner, SKniesel, UKalbacher, HWolburg, H. Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol 2000;79:707–17.Google ScholarPubMed
Lindsay, EA. Chromosomal microdeletions: dissecting del22q11 syndrome. Nature Rev Genet 2001;2:858–68.CrossRefGoogle ScholarPubMed
Liu, HHeath, SCSobin, CRoos, JLGalke, BLBlundell, ML, et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci USA 2002;99:3717–22.CrossRefGoogle Scholar
Morita, KFuruse, MFujimoto, KTsukita, SH. Claudin miltigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci USA 1999a;96:511–6.CrossRefGoogle Scholar
Morita, KSasaki, HFuruse, MTsukita, SH. Endothelial claudin: Claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 1999b;147:185–94.CrossRefGoogle Scholar
Murphy, KC. Schizophrenia and velo-cardio-facial syndrome. Lancet 2002;359:426–30.CrossRefGoogle ScholarPubMed
Park, TWYoon, KSKim, JHPark, WYHirvonen, AKang, D. Functional catechol-O-methyltransferase gene polymorphism and susceptibility to schizophrenia. Eur Neuropsychopharmacol 2002;12:299–303.CrossRefGoogle Scholar
Poliak, SMatlis, SUllmer, CScherer, SPeles, E. Distinct claudins and associated PDZ proteins from different autotypic tight junctions in myelinated Schwann cells. J Cell Biol 2002;159:361–72.CrossRefGoogle Scholar
Pulver, AEKarayiorgou, MWolyniec, PLasseter, VKKasch, LNestadt, G, et al. Sequential strategy to identify a susceptibility gene for schizophrenia: report of Potential linkage on chromosome 22q12-3.1: part 1. Am J Med Genet 1994;54:36–43.CrossRefGoogle ScholarPubMed
Pulver, AEKarayiorgou, MLasseter, VKWolyniec, PKasch, LAntonarakis, S, et al. Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-3.1: part 2. Am J Med Genet 1994;54:44–50.CrossRefGoogle ScholarPubMed
Rahner, CMitic, LLAnderson, JM. Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas and gut. Gastroenterology 2001;120:411–22.CrossRefGoogle ScholarPubMed
Shifman, SBronstein, MSternfeld, MPisante-Shalom, ALev-Leham, EWeizman, A, et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002;71:1296–302.CrossRefGoogle Scholar
Simon, DBLu, YChoate, KAVelazquez, H, Al-Sabban, EPraga, M, et al. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 1999;285:103–6.CrossRefGoogle ScholarPubMed
Singh, MMKay, SR. Wheat gluten as a pathogenic factor in schizophrenia. Science 1976;191:401–2.CrossRefGoogle Scholar
Spielman, RSMcGinnis, REwens, WJ. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;52:506–16.Google Scholar
Storms, LHClopton, JMWright, C. Effects of gluten on schizophrenics. Arch Gen Psychiatr 1982;39:323–7.CrossRefGoogle ScholarPubMed
Terwilliger, JDOtt, J. Linkage disequilibrium between alleles at marker loci. 1st ed. Handbook for Human Genetic Linkage. Baltimore: Johns Hopkins University Press; 1994. p. 188–98.Google Scholar
Tsukita, SHFuruse, M. Occludin and claudins in tight junction strands: leading or supporting players? Trends Cell Biol 1999;9:268–73.CrossRefGoogle ScholarPubMed
Yamagishi, HGarg, VMatsuoka, RThomas, TSrivastava, D. A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects. Science 1999;283:1158–61.Google ScholarPubMed
Yamamoto, KBloom, DLa, STurecki, GJoober, RYamamoto, K, et al. Polymorphism in the cell division cycle 45 like gene and schizophrenia. Am J Med Genet 2001;105:214–5.CrossRefGoogle Scholar
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