A naturally occurring null variant of the NMDA type glutamate receptor NR3B subunit is a risk factor of schizophrenia

PloS One
Hitomi MatsunoYasunori Hayashi

Abstract

Hypofunction of the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been implicated in the pathogenesis of schizophrenia. Here, we investigated the significance of a common human genetic variation of the NMDAR NR3B subunit that inserts 4 bases within the coding region (insCGTT) in the pathogenesis of schizophrenia. The cDNA carrying this polymorphism generates a truncated protein, which is electrophysiologically non-functional in heterologous expression systems. Among 586 schizophrenia patients and 754 healthy controls, insCGTT was significantly overrepresented in patients compared to controls (odds ratio = 1.37, p = 0.035). Among 121 schizophrenia patients and 372 healthy controls, genetic analyses of normal individuals revealed that those carrying insCGTT have a predisposition to schizotypal personality traits (F1,356 = 4.69, p = 0.031). Furthermore, pre-pulse inhibition, a neurobiological trait disturbed in patients with schizophrenia, was significantly impaired in patients carrying insCGTT compared with those with the major allele (F1,116 = 5.72, p = 0.018, F1,238 = 4.46, p = 0.036, respectively). These results indicate that a naturally occurring null variant in NR3B could be a risk factor of schizophrenia.

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Citations

Jun 18, 2016·Frontiers in Physiology·Paula F KinoshitaCristoforo Scavone
Aug 26, 2016·Nature Reviews. Neuroscience·Isabel Pérez-OtañoJohn F Wesseling
Mar 14, 2016·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Yan ZhangMinghua Wu
Apr 24, 2015·Molecular Pharmacology·Hongjie YuanStephen F Traynelis
Oct 28, 2015·Nature Neuroscience·Won-Suk ChungBeth Stevens
Jul 1, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Adriana LoriKerry J Ressler

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Methods Mentioned

BETA
Co-immunoprecipitation
PCR
transfection

Software Mentioned

PASW Statistics
SNPAlyze
SPSS
DYNACOM

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