Association of the soluble CTLA4 with schizophrenia: an observational study

Abstract

Abstract Objective: The immune system is involved in the pathogenesis of schizophrenia; here, we aimed to explore the relationship of cytotoxic T lymphocyte antigen 4 (CTLA4) with schizophrenia. Methods: CTLA4 gene structure was first analyzed, and then rs231779, rs733618, rs231775 and rs3087243 were selected as tag single nucleotide polymorphisms for the linkage disequilibrium blocks in CTLA4 in the Chinese Han population to study expression quantitative trait loci of CTLA4 gene in normal brain tissue. Additionally, membrane CTLA4 (mCTLA4) and soluble CTLA4 (sCTLA4) mRNA expression levels were evaluated in peripheral blood mononuclear cells from 65 first-episode schizophrenia patients and 61 healthy controls. This study was approved by the Bioethics Committee of corresponding research institutes (approval No. 20150016) on March 6, 2015 and the principles of the Declaration of Helsinki. Results: After applying Bonferroni correction to the P values, only the minor C allele of rs733618 was significantly associated with increased expression of total CTLA4 (P Bonf. = 0.019), but not mCTLA4 (P Bonf. = 0.115), in the hippocampus. The sCTLA4 expression was significantly decreased in the peripheral blood mononuclear cells of schizophrenia patients compared with healthy controls, while mCTLA4 was not. Conclusion: These results suggest that the soluble form of CTLA4 may be associated with schizophrenia and that lower sCTLA4 expression may increase the risk of developing schizophrenia.