Genetic variation of GRIN1 confers vulnerability to methamphetamine-dependent psychosis in a Thai population

GRIN1 is a gene that encodes the N-methyl-d aspartate (NMDA) receptor subunit1 (NR1). Variations of GRIN1 have been identified as a risk factor for schizophrenia and drug dependence, supporting hypotheses of glutamatergic dysfunction in these disorders. Methamphetamine (METH) is a psychostimulant drug which can induce psychotic symptoms reminiscent of those found in schizophrenia; thus GRIN1 is a candidate gene for vulnerability to METH dependence or METH-dependent psychosis. The present study examined two polymorphisms of GRIN1, rs11146020 (G1001C) and rs1126442 (G2108A), in 100 male Thai METH-dependent patients and 103 healthy controls using PCR-RFLP techniques. Neither polymorphism was significantly associated with METH dependence, although rs1126442 was highly significantly associated with METH-dependent psychosis, in which the A allele showed reduced frequency (P < 0.00001). The present findings indicate that the rs1126442 of GRIN1 contributes to the genetic vulnerability to psychosis in METH-dependent subjects in the Thai population.