Glutamate Cysteine Ligase Modifier (GCLM) Subunit Gene Is Not Associated with Methamphetamine-Use Disorder or Schizophrenia in the Japanese Population

A recent study showed a significant association between schizophrenia in European samples and the glutamate cysteine ligase modifier (GCLM) subunit gene, which is the key glutathione (GSH)-synthesizing enzyme. Since the symptoms of methamphetamine (METH)-induced psychosis are similar to those of schizophrenia, the GCLM gene is thought to be a good candidate gene for METH-use disorder or related disorders. To evaluate the association between the GCLM gene and METH-use disorder and schizophrenia, we conducted a case-control study of Japanese subjects (METH-use disorder, 185 cases; schizophrenia, 742 cases; and controls, 819). Four SNPs (2 SNPs from an original report and JSNP database, and 2 tagging SNPs from HapMap database) in the GCLM gene were examined in this association analysis; one SNP showed an association with both METH-use disorder and METH-induced psychosis. After Bonferroni's correction for multiple testing, however, this significance disappeared. No significant association was found with schizophrenia. Our findings suggest that a common genetic variation in the GCLM gene might not contribute to the risk of METH-use disorder and schizophrenia in the Japanese population.