Genetic Association Analysis of NOS3 and Methamphetamine-Induced Psychosis Among Japanese

Y.      Fukuo; N.      Iwata; H.      Ujike; N.      Ozaki; I.      Sora; M.      Iyo; N.      Uchimura; M.      Yamada; T.      Inada; T.      Okochi; T.      Tsunoka; T.      Okumura; K.      Kawashima; Y.      Kinoshita; T.      Kitajima; M.      Ikeda; T.      Kishi

Abstract

Endothelial nitric oxide synthase (NOS3) is one of the enzymes influencing nitric oxide (NO) function in the human brain. NO is a gaseous neurotransmitter that is involved in a variety of mechanisms in the central nervous system, such as N-methyl-D-aspartate receptor activation and oxidative stress. The evidence from animal pharmacological studies and postmortem studies supports an association between NO and psychotic disorders. Methamphetamine (METH) use disorder is a known psychotic disorder, and we therefore conducted a gene-based case-control study between tagging single nucleotide polymorphisms (SNPs) (rs2070744, rs1799983) in NOS3 and METH-induced psychosis in Japanese subjects (183 with METH-induced psychosis and 267 controls). Written informed consent was obtained from each subject. No significant association was found between any tagging SNP in NOS3 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, we suggest that NOS3 might not contribute to the risk of METH-induced psychosis in the Japanese population.

Keywords: Methamphetamine-induced psychosis, endothelial nitric oxide synthase (NOS3), gene-based case-control association study, endothelial nitric oxide synthase, (NOS3), gene-based case-control association Study, psychiatric disorder, dopaminergic neurotoxicity, schizophrenia, neuronal dysfunction, behavioral abnormality