An association study between PPP1R1B gene and schizophrenia in the Chinese population

Abstract

Schizophrenia has been linked with dysfunctions of glutamatergic, dopaminergic, and serotonergic neurotransmission. Dopamine- and cAMP-regulated phosphoprotein of relative molecular mass 32 kDa (DARPP-32), encoded by PPP1R1B (protein phosphatase 1, regulatory/inhibitor subunit 1B) gene, is enriched in neostriatal medium spiny neurons. It plays a key regulator role in dopaminergic and glutamatergic signaling pathways. The combined evidence from reduced DARPP-32 expression in the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients and from abnormalities in mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32 suggested that it would be worthwhile to investigate the association between DARPP-32 and schizophrenia. In the present study, we genotyped five single nucleotide polymorphisms (SNPs) in the PPP1R1B gene and conducted a case-control study involving 520 schizophrenic patients and 386 healthy subjects drawn from the Chinese population. No allelic, genotypic or haplotypic association was found. However, our results do not preclude the possibility that the PPP1R1B is a susceptibility gene for schizophrenia in the Chinese population, since, as a central molecular switch, PPP1R1B may contribute to schizophrenia by interacting with other genes. Further functional analysis and genetic association studies are needed to determine the potential roles of PPP1R1B and other related genes in the pathophysiology of schizophrenia.