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Article: Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia

TitleFunctional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia
Authors
KeywordsAdipokines
Adult
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/physiology
Case-Control Studies
Cell Line
China
Female
Genes, myc/physiology
Genetic Predisposition to Disease
Glycoproteins/*genetics/metabolism
*Haplotypes
Humans
Lectins
Male
Middle Aged
Promoter Regions, Genetic
Protein Binding
Schizophrenia/*genetics
Signal Transduction
Transcriptional Activation
Issue Date2007
Citation
American Journal of Human Genetics, 2007, v. 80 n. 1, p. 12-18 How to Cite?
AbstractThe chitinase 3-like 1 gene (CHI3L1) is abnormally expressed in the hippocampus of subjects with schizophrenia and may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia. Here, we provide evidence that the functional variants at the CHI3L1 locus influence the genetic risk of schizophrenia. First, using case-control and transmission/disequilibrium-test (TDT) methodologies, we detected a significant association between schizophrenia and haplotypes within the promoter region of CHI3L1 in two independent cohorts of Chinese individuals. Second, the at-risk CCC haplotype (P=.00058 and .0018 in case-control and TDT studies, respectively) revealed lower transcriptional activity (P=2.2 x 10(-7)) and was associated with lower expression (P=3.1 x 10(-5)) compared with neutral and protective haplotypes. Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype. In contrast, the protective TTG haplotype was associated with a high level of CHI3L1 expression. Our findings identify CHI3L1 as a potential schizophrenia-susceptibility gene and suggest that the genes involved in the biological response to adverse environmental conditions are likely to play roles in the predisposition to schizophrenia.
Persistent Identifierhttp://hdl.handle.net/10722/208437
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, Xen_US
dc.contributor.authorTang, Ren_US
dc.contributor.authorGao, Ben_US
dc.contributor.authorShi, Yen_US
dc.contributor.authorZhou, Jen_US
dc.contributor.authorGuo, Sen_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorTang, Wen_US
dc.contributor.authorMeng, Jen_US
dc.contributor.authorLi, Sen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorMa, Gen_US
dc.contributor.authorLin, Cen_US
dc.contributor.authorXiao, Yen_US
dc.contributor.authorFeng, Gen_US
dc.contributor.authorLin, Zen_US
dc.contributor.authorZhu, Sen_US
dc.contributor.authorXing, Yen_US
dc.contributor.authorSang, Hen_US
dc.contributor.authorSt Clair, Den_US
dc.contributor.authorHe, Len_US
dc.date.accessioned2015-03-11T03:00:57Z-
dc.date.available2015-03-11T03:00:57Z-
dc.date.issued2007en_US
dc.identifier.citationAmerican Journal of Human Genetics, 2007, v. 80 n. 1, p. 12-18en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/208437-
dc.description.abstractThe chitinase 3-like 1 gene (CHI3L1) is abnormally expressed in the hippocampus of subjects with schizophrenia and may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia. Here, we provide evidence that the functional variants at the CHI3L1 locus influence the genetic risk of schizophrenia. First, using case-control and transmission/disequilibrium-test (TDT) methodologies, we detected a significant association between schizophrenia and haplotypes within the promoter region of CHI3L1 in two independent cohorts of Chinese individuals. Second, the at-risk CCC haplotype (P=.00058 and .0018 in case-control and TDT studies, respectively) revealed lower transcriptional activity (P=2.2 x 10(-7)) and was associated with lower expression (P=3.1 x 10(-5)) compared with neutral and protective haplotypes. Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype. In contrast, the protective TTG haplotype was associated with a high level of CHI3L1 expression. Our findings identify CHI3L1 as a potential schizophrenia-susceptibility gene and suggest that the genes involved in the biological response to adverse environmental conditions are likely to play roles in the predisposition to schizophrenia.en_US
dc.languageengen_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.subjectAdipokinesen_US
dc.subjectAdulten_US
dc.subjectBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/physiologyen_US
dc.subjectCase-Control Studiesen_US
dc.subjectCell Lineen_US
dc.subjectChinaen_US
dc.subjectFemaleen_US
dc.subjectGenes, myc/physiologyen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGlycoproteins/*genetics/metabolismen_US
dc.subject*Haplotypesen_US
dc.subjectHumansen_US
dc.subjectLectinsen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectPromoter Regions, Geneticen_US
dc.subjectProtein Bindingen_US
dc.subjectSchizophrenia/*geneticsen_US
dc.subjectSignal Transductionen_US
dc.subjectTranscriptional Activationen_US
dc.titleFunctional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophreniaen_US
dc.typeArticleen_US
dc.identifier.emailGao, B: gaobo@hku.hken_US
dc.identifier.authorityGao, B=rp02012en_US
dc.identifier.doi10.1086/510438en_US
dc.identifier.pmid17160890-
dc.identifier.scopuseid_2-s2.0-33846005875-
dc.identifier.volume80en_US
dc.identifier.issue1en_US
dc.identifier.spage12en_US
dc.identifier.epage18en_US
dc.identifier.isiWOS:000243102500002-

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