BACKGROUND
Schizophrenia is a complex and debilitating mental disorder with a strong heritability. Immune imbalance is considered to be an important pathogenesis. Interleukin 15 and interleukin 15 receptor alpha are classic immune molecule and also maintains normal brain function, but little is known whether IL-15RA variants contribute to the pathogenesis of schizophrenia.
OBJECTIVE
Testing the hypothesis that the genetic variants of IL-15RA are associated with schizophrenia progression and that IL-15RA SNPs play key roles in the downstream signaling transduction.
METHODS AND RESULTS
We sequenced IL-15RA exon from 132 Chinese schizophrenic patients and discovered a rare variants(rs528238821)in a patient who is catatonic schizophrenia with ankylosing spondylitis and his clinical features is similar to phenotype of IL-15Rα KO mice. Furthermore, the pBI-CMV vector over expressed missense variant significantly increased IL-15Rα expression in vitro. Cells carrying this mutation showed an attenuated response to exogenous interleukin15 stimulation through the inhibition of STAT3 phosphorylation.
CONCLUSION
We report this rare variant exists in schizophrenic patients and interferes with IL-15Rα intracellular signal transduction which may be a suspicious variant for specific types of schizophrenia.