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Recent preclinical findings that repeated treatment with methamphetamine (METH) induced an increase in tumor necrosis factor-α (TNF-α) mRNA in some brain regions and that TNF-α blocked METH neurotoxicity and rewarding effects suggest TNF-α, a multifunctional pro-inflammatory cytokine, may be involved in METH dependence. We hypothesized that genetic polymorphisms of the TNF-α gene and its receptor genes may be associated with vulnerability to METH dependence. Genetic association of -308G>A and -857C>T in the promotor region of the TNF-α gene, and 36A>G in exon 1 of the TNF receptor 1A gene (TNFR-SF1A), were analyzed in patients with METH dependence ( n= 185) and healthy controls ( n= 221) in a Japanese population. No significant association of alleles or haplotypes of the TNF-α or TNFR-SF1A genes with METH dependence was found. Neither was any significant association of clinical phenotype with METH dependence found. These results suggest that genetic variations in the TNF-α gene and its receptor genes may not be involved in individual vulnerability to METH dependence. [ABSTRACT FROM AUTHOR]

Cocaine- and amphetamine-regulated transcript (CART) was originally discovered as a peptide that increased in the rat striatum after injection of a psychostimulant drug, such as cocaine or amphetamine, and is suggested to play potential roles in drug dependence. We tested the genetic association between the CART gene and methamphetamine (METH) dependence and/or psychosis. The subjects were 203 patients with METH dependence and 239 age- and gender-matched healthy controls. Two single nucleotide polymorphisms (SNPs) of the CART gene, −156A>G and IVS1 + 224G>A, were examined . There were no significant differences in genotype and allele distributions of the polymorphisms between patients with METH dependence and/or psychosis and controls. Neither were significant differences in subgroups of clinical phenotypes, for example, age at first consumption of METH, latency to onset of psychotic symptoms after the first consumption of METH, prognosis of psychosis after therapy, complication of spontaneous relapse to a psychotic state, or multisubstance abuse status, observed. The present findings suggest that the CART gene may not play a pivotal role in the development of METH dependence and psychosis, at least in a Japanese population. [ABSTRACT FROM AUTHOR]