Association Study of Genetic Variants in SOD2 and DTNBP1 with Methamphetamine Psychosis

Objective. This study aimed to 1) compare the distribution of genetic variants in SOD2 and DTNBP1 between methamphetamine (METH) users who had psychosis and those who did not have psychosis; and 2) evaluate whether the relations of these genetic variants to METH-induced psychosis remained after adjustment for other known correlates of METH-induced psychosis. Methods. The study sample consisted of 84 cases with METH-induced psychosis and 187 controls of METH users without psychosis, recruited from Taipei City Psychiatric Center and Taipei Detention Center. Five single nucleotide polymorphisms (SNPs) of SOD2 and three SNPs of DTNBP1 were genotyped. Both single locus and haplotype analyses were conducted with adjustment for multiple comparison using effective number of markers, and then multivariable logistic regression analyses were used to adjust for age, sex, and duration of METH use. Potential gene-gene interaction was examined using the generalized multifactor dimensionality reduction method. Results. None of the individual SNPs were associated with METH-induced psychosis after adjustment for multiple comparisons. For subgroup analysis, both rs4880 and rs2855116 of SOD2 were significantly associated with the prolonged METH-induced psychosis. Under the assumption of codominant model, the CC genotype of rs4880 was significantly associated with METH-induced psychosis after adjustment of age, sex and METH use duration. In haplotype analyses, neither SOD2 nor DTNBP1 was significantly associated with development of methamphetamine psychosis. Gene-gene interaction was non-significant. Conclusions. Our results suggest that the C-allele of rs4880 on SOD2 was associated with METH-induced psychosis, particularly for the prolonged psychosis. The finding implies further investigation on the role of oxidative stress mechanism in the development of METH-induced psychosis is warranted