Interaction between genetic variants of DLGAP3 and SLC1A1 affecting the risk of atypical antipsychotics-induced obsessive-compulsive symptoms.

Adverse effects of atypical antipsychotics (AAP) can include obsessive-compulsive (OC) symptoms. Based on biological evidence of the relationship between the glutamatergic system and both OC disorder and AAP, this study aimed to determine whether DLGAP3, coding a post-synaptic scaffolding protein of glutamatergic synapses, is associated with AAP-induced OC symptoms. Furthermore, we explored the interactions between DLGAP3 and a previously reported susceptibility gene, the glutamate transporter gene SLC1A1, regarding this phenotype. Subjects were clinically stable schizophrenia patients receiving AAP treatment (n = 94), and they comprised an OC group (n = 40) and a non-OC group (n = 54) (patients with and without AAP-induced OC symptoms, respectively). We performed allelic/genotypic/haplotype association analyses for seven tag single-nucleotide polymorphisms of DLGAP3 and gene-gene interaction analyses with rs2228622 of SLC1A1, observing a nominally significant association between AAP-induced OC symptoms and rs7525948 in both simple chi-square tests and the regression analyses (nominal P < 0.05). In the logistic regression analysis of gene-gene interaction, we found a significant interaction effect of rs7525948 of DLGAP3 and rs2228622 of SLC1A1 (permutation P = 0.036) on AAP-induced OC symptoms, with a 30.2 times higher odds for individuals carrying risk genotypes at both loci in comparison with the reference group, which had no risk genotypes. This study provides suggestive evidence that DLGAP3 and its interactive effect with SLC1A1 might be involved in susceptibility to developing OC symptoms in schizophrenia patients receiving AAP treatment.