Association Analysis of the Tryptophan Hydroxylase 2 Gene Polymorphisms in Patients with Methamphetamine Dependence/Psychosis

Hideaki      Kobayashi; Hiroshi      Ujike; Nakao      Iwata; Toshiya      Inada; Mitsuhiko      Yamada; Yoshimoto      Sekine; Naohisa      Uchimura; Masaomi      Iyo; Norio      Ozaki; Masanari      Itokawa; Ichiro      Sora

doi:10.2174/157015911795017335

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.

Keywords: Single nucleotide polymorphism, SNP, variation, serotonin, human, Japanese, MAP, abuse, polymorphism, AP, nucleotide polymorphisms, polymorphic variants