Association analysis of GRM2 and HTR2A with methamphetamine-induced psychosis and schizophrenia in the Japanese population

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2010-05, Vol.34 (4), p.639-644
• Main Authors: Tsunoka, Tomoko, Kishi, Taro, Kitajima, Tsuyoshi, Okochi, Tomo, Okumura, Takenori, Yamanouchi, Yoshio, Kinoshita, Yoko, Kawashima, Kunihiro, Naitoh, Hiroshi, Inada, Toshiya, Ujike, Hiroshi, Yamada, Mitsuhiko, Uchimura, Naohisa, Sora, Ichiro, Iyo, Masaomi, Ozaki, Norio, Iwata, Nakao
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Amphetamine-Related Disorders - genetics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Case-Control Studies; Functional SNP; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Glutamate metabotropic receptor 2 gene ( GRM2); Haplotypes; Humans; Japan; Medical sciences; Methamphetamine - adverse effects; Methamphetamine-induced psychosis; Mutation; Neuropharmacology; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychoses, Substance-Induced - genetics; Receptor, Serotonin, 5-HT2A - genetics; Receptors, Metabotropic Glutamate - genetics; Regression Analysis; Schizophrenia; Schizophrenia - genetics; Serotonin receptor 2A gene ( HTR2A); Tagging SNP
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2010.03.002

Abnormalities in glutaminergic neural transmission have been suggested to be involved in the pathogenesis of schizophrenia. A recent study reported that alterations in the 5-HT2A–mGluR2 complex may be involved in neural transmission in the schizophrenic cortex. In addition, methamphetamine-induced psychosis is thought to be similar to schizophrenia. Therefore, we conducted a case-control study with Japanese samples (738 schizophrenia patients, 196 methamphetamine-induced psychosis patients, and 802 controls) to evaluate the association and interaction between GRM2, HTR2A and schizophrenia. We selected three ‘tagging SNPs’ in GRM2, and two biologically functional SNPs in HTR2A (T102C and A1438G), for the association analysis. We detected a significant association between methamphetamine-induced psychosis and GRM2 in a haplotype-wise analysis, but not HTR2A. We did not detect an association between GRM2 or HTR2A and schizophrenia. In addition, no interactions of GRM2 and HTR2A were found in methamphetamine-induced psychosis or schizophrenia. We did not detect any novel polymorphisms in GRM2 when we performed a mutation search using methamphetamine-induced psychosis samples. Our results suggested that GRM2 may play a role in the pathophysiology of methamphetamine-induced psychosis but not schizophrenia in the Japanese population. A replication study using larger samples or samples of other populations will be required for conclusive results.