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Current Molecular Medicine

Author(s): Yanli Pan, Zhimin Wang, Guangping Zhang, Junhua Guo, Xuequan Zhu, Jia Zhou, Zhenrong Zhang, Zuoli Sun, Jian Yang, Abba J. Kastin, Weihong Pan, Xiaojun Wu, Jianliang Zhang, Xiaomin Wang, Chuanyue Wang and Yi He*

DOI: 10.2174/1566524019666190617172054

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Schizophrenia Patient Shows a Rare Interleukin 15 Receptor alpha Variant Disrupting Signal Transduction

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Abstract

Background: Schizophrenia is a complex and debilitating mental disorder with strong heritability. Its pathogenesis involves immune dysregulation. Interleukin 15 and interleukin 15 receptor alpha(IL-15Rα) are classical immune molecules. They also help maintain normal brain function, leading to our hypothesis that IL-15Rα gene(IL- 15RA) variants contribute to the pathogenesis of schizophrenia.

Objective: We determine whether the genetic variants of IL-15RA are associated with the development and progression of schizophrenia and whether IL-15RA single nucleotide polymorphism(SNP) plays a key role in downstream signaling transduction.

Methods and Results: We sequenced IL-15RA exon from 132 Chinese schizophrenic patients and identified a rare variant(rs528238821) in a patient diagnosed with catatonic schizophrenia and ankylosing spondylitis(AS). We overexpressed this missense variant in cells driven by pBI-CMV vector. The cells showed attenuated STAT3 phosphorylation in response to interleukin15.

Conclusion: IL-15RA mutation is rare in schizophrenic patients but interfered with IL- 15Rα intracellular signal transduction. Given the similarity of symptoms of catatonic schizophrenia and the known phenotype of IL-15Rα knockout mice, gene variation might offer diagnostic value for sub-types of schizophrenia.

Keywords: Interleukin 15 receptor alpha, interleukin 15, single nucleotide polymorphism, schizophrenia, IL-15RA, STAT3 phosphorylation.

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