Functional Variants in the Promoter Region of Chitinase 3-like 1 (CHI3L1) and Susceptibility to Schizophrenia

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2006 Dec 13

PMID 17160890

Citations 29

Authors

Xinzhi Zhao

Ruqi Tang

Bo Gao

Yongyong Shi

Jian Zhou

Shengzhen Guo

Jing Zhang

Yabing Wang

Wei Tang

Junwei Meng

Sheng Li

Hongsheng Wang

Gang Ma

Chuwen Lin

Yue Xiao

Guoyin Feng

Zhiguang Lin

Shaomin Zhu

Yangling Xing

Hong Sang

David St Clair

Lin He

Affiliations

Soon will be listed here.

Abstract

The 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.

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