Abstract
There is a growing evidence that serotoninergic systems modulate dopaminergic neurotransmission. We analyzed the association between the variations in the brain tryptophan hydroxylase 2 (TPH2) gene, a rate limiting enzyme for serotonin biosynthesis, and methamphetamine (METH) dependence/psychosis in a Japanese population. We found ten single nucleotide polymorphisms (SNPs) and two polynucleotide polymorphisms in TPH2 gene exons and exon-intron boundaries. A total of 162 patients and 243 controls were used for the association analysis between these polymorphisms and METH dependence/psychosis. No significant differences were observed in either genotypic or allelic frequencies between METH dependent/psychotic patients and controls. A global test of differentiation among samples based on haplotype frequencies showed no significant association. With respect to latency of psychosis, prognosis of psychosis, and spontaneous relapse, we found no significant association with these SNPs. These results suggest that the TPH2 gene variants may not be a factor in vulnerability to METH dependence/psychosis.
Highlights
Methamphetamine (METH) is a psychomotor stimulant with high liability for abuse, and METH abuse has become a very serious social problem in Japan [1]
linkage disequilibrium (LD) mapping was analyzed by using single nucleotide polymorphisms (SNPs) having minor allele frequencies of over 10% in both samples (Table 4)
We failed to identify any variants or haplotypes in the tryptophan hydroxylase 2 (TPH2) gene examined in this study which were associated with METH dependence/psychosis
Summary
Methamphetamine (METH) is a psychomotor stimulant with high liability for abuse, and METH abuse has become a very serious social problem in Japan [1]. Associations have been observed between TPH2 variants and bipolar disorder [13,14,15,16,17,18], suicidal behavior in major depression [19,20,21], the response to selective serotonin reuptake inhibitors (fluoxetine and/or citalopram) [22, 23] and emotional regulation in healthy subjects [24,25,26,27,28] These reports indicate that polymorphic variants in the TPH2 gene may have a role in the pathophysiology of a wide range of psychiatric disorders and emotional regulation. A recent study of heroin addiction showed an association with TPH2 variants in Hispanics and AfricanAmericans [29]
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