Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations

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.

In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases

“…Moreover, two genetic studies claimed that variants in the promoter of CHI3L1 are associated with susceptibility to schizophrenia [ 19 , 20 ]. However, a more recent study failed to confirm a genetic association between CHI3L1 and schizophrenia in Japanese and Chinese populations [ 21 ]. Overall, our results showed only occasional CHI3L1 positive cells in schizophrenia.…”

Correlation of Chitinase 3-Like 1 Single Nucleotide Polymorphisms with Hepatocellular Carcinoma in Taiwan

“…However, the rs10399805 polymorphism has been found to be associated with diseases such as atopy and schizophrenia 32 , 54 . Regarding rs6691378 and rs10399805, the genetic contribution of CHI3L1 to schizophrenia has been shown to vary, despite it being mechanistically involved in the disease process 55 . In addition, our previous study demonstrated that the CHI3L1 SNPs rs6691378 and rs10399805 and the CHI3L1 haplotype correlate with the development of cervical precancerous lesions and invasive cancer 33 .…”

Allelic expression imbalance of the schizophrenia susceptibility gene CHI3L1

“…The precise role of CHI3L1 is unknown; however, it is believed to play a role in cell survival by mediating cellular response to physiological insults. The associations were not replicated in a study including Chinese and Japanese individuals (Yamada et al, 2009). In addition, the induction of CHI3L1 is thought to be indicative of tissue remodelling in rheumatoid joints (Johansen et al, 1993), and it is speculated that this role may extend to remodelling of neuronal connections in the brain (Chung et al, 2003).…”