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Relations of Genetic Variants in Superoxide Dismutase 2 and Dystrobrevin-binding Protein 1 to Methamphetamine Psychosis among Methamphetamine Dependents in Taiwan

Ying-Ching Lai, Shih-Ku Lin, Ming-Chyi Huang, Hsing-Cheng Liu, Yen-Lung Chiou, Chun-Hsin Chen, Wei J. Chen

Objectives: Both superoxide dismutase 2 gene (SOD2), encoding a free radical scavenger, and dystrobrevin-binding protein 1 gene (DTNBP1), a candidate gene for schizophrenia, have been implicated in methamphetamine (METH) psychosis. In this study, we intended to compare the distribution of those two genes between METH users with and without psychosis and to evaluate whether the length of time of METH exposure influenced such relationship. Methods: The study sample consisted of 84 cases of patients with METH-induced psychosis and 187 controls (METH users without psychosis). Five single-nucleotide polymorphisms (SNPs) in SOD2 and three SNPs in DTNBP1 were genotyped. We did both single-locus and haplotype analyses, and adjusted for multiple comparisons with an effective number of markers, and multivariable logistic regression analyses for adjusting for age, sex, and duration of METH use. Results: None of the individual SNPs were associated with METH-induced psychosis after adjustment for multiple comparisons. In the subgroup analysis, both rs4880 and rs2855116 in SOD2 were significantly associated with prolonged METH-induced psychosis (p < 0.01 and p < 0.01, respectively). Under the assumption of a codominant model, the CC genotype of rs4880 was significantly associated with METH-induced psychosis after adjustments for age, sex, and the duration of METH use (p < 0.01). This association was not supported by the haplotype analyses or gene–gene interactions between SOD2 and DTNBP1. Conclusion: Functional C-allele of rs4880 in SOD2 was associated with the prolonged subtype of METH-induced psychosis in Taiwanese population. Oxidative stress mechanisms show a rôle in the development of METH-induced psychosis.
Key Word oxidative stress, polymorphism, reactive oxygen species, scavenger
Editorial Committe, Taiwanese Journal of Psychiatry
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