Association study of the vesicular monoamine transporter 1 (VMAT1) gene with schizophrenia in a Japanese population

Abstract

BackgroundVesicular monoamine transporters (VMATs) mediate accumulation of monoamines such as serotonin, dopamine, adrenaline, and noradrenaline from the cytoplasm into storage organelles. The VMAT1 (alternatively solute carrier family 18: SLC18A1) regulates such biogenic amines in neuroendocrine systems. The VMAT1 gene maps to chromosome 8p21.3, a locus with strong evidence of linkage with schizophrenia. A recent study reported that a non-synonymous single nucleotide polymorphism (SNP) of the gene (Pro4Thr) was associated with schizophrenia.MethodsWe attempted to replicate this finding in a Japanese sample of 354 schizophrenics and 365 controls. In addition, we examined 3 other non-synonymous SNPs (Thr98Ser, Thr136Ile, and Val392Leu). Genotyping was performed by the TaqMan allelic discrimination assay.ResultsThere was no significant difference in genotype or allele distribution of the three SNPs of Pro4Thr, Thr136Ile, or Val392Leu between patients and controls. There was, however, a significant difference in genotype and allele distributions for the Thr98Ser polymorphism between the two groups (P = 0.01 for genotype and allele). When sexes were examined separately, significant differences were observed in females (P = 0.006 for genotype, P = 0.003 for allele), but not in males. The Thr98 allele was more common in female patients than in female controls (odds ratio 1.69, 95% CI 1.19–2.40, P = 0.003). Haplotype-based analyses also provided evidence for a significant association in females.ConclusionWe failed to replicate the previously reported association of Pro4Thr of the VMAT1 gene with schizophrenia. However, we obtained evidence for a possible role of the Thr98Ser in giving susceptibility to schizophrenia in women.

Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing

“…Given previous associations between Thr136Ile genotype and BPD 27 as well as both Thr4Pro and Ser98Thr genotypes with SZ 23 – 26 we used a translational research approach to investigate potential functional effects of these variants. Full length human VMAT1 cDNA is expressed in substantia nigra and was cloned for subsequent experiments ( Fig.…”

“…In this paper we focus on VMAT1 which has recently emerged as a candidate gene for neuropsychiatric disorders. Several reports have shown that common missense variants in VMAT1 are associated with bipolar disorder (BPD), schizophrenia (SZ), anxiety-related personality traits and cognitive phenotypes related to SZ 23 – 29 . This is remarkable since the VMAT1 gene is located on chromosome 8p, a region previously implicated as a shared genomic susceptibility region for SZ/BPD in linkage scans.…”

Altered expression of mRNA profiles in blood of early-onset schizophrenia

“…SLC18A1 is mapped to chromosome 8p21.3, a locus with strong evidence for linkage with SZ 22 23 . SLC18A1 has been reported to be associated with SZ 24 25 26 27 . In this study, we detected an increased level of expression of SLC18A1 in SZ patients, providing further support for its possible involvement into SZ.…”

Assessment of individual differences in the rat nucleus accumbens transcriptome following taste-heroin extended access

“…Deletion of Slc18a1 in mice reduces hippocampal neurogenesis and produces neurocognitive deficits [26]. Furthermore mutations in the Slc18a1 gene also have been linked to an increased likelihood of developing schizophrenia [33] and type 1 bipolar disease [20]. The decreased expression of this gene in the Large Suppressor group may reflect blunted synaptic plasticity in the nucleus accumbens; a difference which could contribute to the addiction phenotype.…”