Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] Journal article | | Title | Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. | | Author(s) | Yamada K, Hattori E, Iwayama Y, Toyota T, Ohnishi T, Iwata Y, Tsuchiya KJ, Sugihara G, Kikuchi M, Okazaki Y, Yoshikawa T | | Institution | Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan. | | Source | Am J Med Genet B Neuropsychiatr Genet 2008 Sep 2. | | Abstract | Recently, three common polymorphisms in the promoter region of the Chitinase 3-Like 1 (CHI3L1) gene, rs6691378, rs10399805 and rs4950928, have been identified as schizophrenia predisposing single nucleotide polymorphisms (SNPs) in the Han Chinese population. The at-risk haplotype comprising these SNPs was also related to decreased expression of CHI3L1 in peripheral blood cells. In contrast, two independent postmortem brain studies have reported elevated expression of the transcript in the hippocampus and prefrontal cortex, from schizophrenic patients. The gene encodes a secreted glycoprotein (HC-gp39 or YKL40), which is deemed to be involved in the inflammatory process. These pieces of evidence signify the potential importance of CHI3L1 in the pathogenesis of schizophrenia. In this study, we aimed to replicate the prior genetic association findings using two sample sets, one set of Chinese samples (293 pedigrees consisting of 1,163 subjects) that are ethnically identical to those used in the original report and a second set from the relatively close Japanese population (570 schizophrenic patients and 570 matched controls). We analyzed the same five SNPs as in the original study, including the three promoter SNPs. None of these SNPs showed association signals with schizophrenia (P values >0.108) in our sample sets. These results suggest that the genetic contribution of CHI3L1 to schizophrenia is variable, even though it is mechanistically involved in the disease process. (c) 2008 Wiley-Liss, Inc. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18767121 |
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