Biological psychiatry · 2008
Chitinase-3-like 1 (CHI3L1) gene and schizophrenia: genetic association and a potential functional mechanism.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yang Mao Sheng, Morris Derek W, Donohoe Gary, Kenny Elaine, O'Dushalaine Colm T, Schwaiger Siobhan, Nangle Jeanne Marie, Clarke Sarah, Scully Paul, Quinn John, Meagher David, Baldwin Patrizia, Crumlish Niall, O'Callaghan Eadbhard, Waddington John L, Gill Michael, Corvin Aiden
Аннотация
BACKGROUND: Gene expression data and association analyses in two Chinese samples implicate chitinase 3-like 1 (CHI3L1), a cellular survival gene, in schizophrenia susceptibility.
METHODS: We tested whether the association data are robust to replication in a Caucasian schizophrenia sample and performed a comprehensive investigation of common genetic variation at the locus.
RESULTS: In a sample of 375 case and 812 control subjects we identified significant association with the same risk allele at the promoter single nucleotide polymorphism (SNP) associated in the original study (rs10399805; p = .018) and with another SNP at intron 7 of CHI3L1 (rs2275351; p = .008). The rs10399805 SNP is located at position -247 and disrupts the C/EBP-AML-1 binding site in the gene promoter; the risk allele is predicted to increase CHI3L1 expression, as has been reported in several postmortem schizophrenia studies. Carriers of the risk variant presented with fewer positive symptoms and relatively spared cognitive performance compared with other schizophrenia patients.
CONCLUSIONS: These findings support a functional mechanism for involvement of CHI3L1 in schizophrenia susceptibility, possibly contributing to a less severe illness. The associated variants in this study are not well tagged by all Whole-Genome Association (WGA) platforms, suggesting additional genotyping may be necessary despite the imminent availability of WGA data from large SZ samples. Because CHI3L1 may be involved in transmission of stress-induced cellular responses, studies of interaction with known environmental risk factors may also be warranted.
METHODS: We tested whether the association data are robust to replication in a Caucasian schizophrenia sample and performed a comprehensive investigation of common genetic variation at the locus.
RESULTS: In a sample of 375 case and 812 control subjects we identified significant association with the same risk allele at the promoter single nucleotide polymorphism (SNP) associated in the original study (rs10399805; p = .018) and with another SNP at intron 7 of CHI3L1 (rs2275351; p = .008). The rs10399805 SNP is located at position -247 and disrupts the C/EBP-AML-1 binding site in the gene promoter; the risk allele is predicted to increase CHI3L1 expression, as has been reported in several postmortem schizophrenia studies. Carriers of the risk variant presented with fewer positive symptoms and relatively spared cognitive performance compared with other schizophrenia patients.
CONCLUSIONS: These findings support a functional mechanism for involvement of CHI3L1 in schizophrenia susceptibility, possibly contributing to a less severe illness. The associated variants in this study are not well tagged by all Whole-Genome Association (WGA) platforms, suggesting additional genotyping may be necessary despite the imminent availability of WGA data from large SZ samples. Because CHI3L1 may be involved in transmission of stress-induced cellular responses, studies of interaction with known environmental risk factors may also be warranted.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAdipokinesAllelesAsian PeopleCell SurvivalChitinase-3-Like Protein 1Core Binding Factor Alpha 2 SubunitCross-Cultural ComparisonFemaleGenetic Carrier ScreeningGenetic Predisposition to DiseaseGenotypeGlycoproteinsHumansLectinsMalePhenotypePolymorphism, Single NucleotidePromoter Regions, GeneticPsychiatric Status Rating ScalesRNA-Binding ProteinsRisk FactorsSchizophreniaSchizophrenic PsychologySocial EnvironmentWhite People