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

Abstract

BACKGROUND:

Vesicular 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.

METHODS:

We 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.

RESULTS:

There 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.

CONCLUSION:

We 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.

• Authors: Misty Richards, Yoshimi Iijima, Hitomi Kondo, Tomoko Shizuno, Hiroaki Hori, Kunimasa Arima, Osamu Saitoh, Hiroshi Kunugi
• Journal: Behavioral and brain functions : BBF (Behav Brain Funct) Vol. 2 Pg. 39 (Nov 30 2006) ISSN: 1744-9081 [Electronic] England
• PMID: 17134514 (Publication Type: Journal Article)