Human GRIK3 blocking peptide

Various studies have been done to check the status of glutamate receptor gene in the pathogenesis of schizophrenia. The T928G (Ser310Ala) polymorphism of ionotropic glutamate receptor kainate 3 gene (GRIK3) and its positive association with schizophrenia was reported in Caucasians, whereas no association of this polymorphism with schizophrenia was shown in two other populations, Chinese and Japanese. However, no literature is available regarding the prevalence of this polymorphism and its association with schizophrenia in the Indian population. As genetic susceptibility profiles in India are often different from those of white Caucasians or Orientals, we investigated the status of Ser310Ala polymorphism of GRIK3 in 100 schizophrenic patients and 100 healthy controls in the Indian population by the PCR-RFLP (restriction fragment length polymorphism) method. A statistically significant difference in the genotype and allelic distributions (P < 0.000001 and P = 0.01, respectively) of Ser310Ala polymorphism was found in schizophrenics than in control, considering Ala-allele as being associated with the disease (OR = 1.7, 95% CI = 1.137 - 2.540). Our study suggests a potential role for GRIK3 for susceptibility to schizophrenia in Indian population.

Obsessive-compulsive disorder (OCD) has been associated with regional volumetric brain abnormalities, which provide promising intermediate phenotypes of the disorder. In this study, volumes of brain regions selected for a priori evidence of association with OCD (orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), thalamus, caudate, putamen, globus pallidus and pituitary) were measured using structural magnetic resonance imaging (MRI) in 20 psychotropic-naive pediatric OCD patients. We examined the association between these regional brain volumes and a total of 519 single nucleotide polymorphisms (SNPs) from nine glutamatergic candidate genes (DLGAP1, DLGAP2, DLGAP3, GRIN2B, SLC1A1, GRIK2, GRIK3, SLITRK1 and SLITRK5). These genes were selected based on either previous reported association with OCD in humans or evidence from animal models of OCD. After correcting for multiple comparisons by permutation testing, no SNP remained significantly associated with volumetric changes. The strongest trend toward association was identified between two SNPs in DLGAP2 (rs6558484 and rs7014992) and OFC white matter volume. Our other top ranked association findings were with ACC, OFC and thalamus. These preliminary results suggest that sequence variants in glutamate candidate genes may be associated with structural neuroimaging phenotypes of OCD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.