Association study of the vesicular monoamine transporter 1 VMAT1 gene with schizophrenia in a Japanese populationReportar como inadecuado

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Behavioral and Brain Functions

, 2:39

First Online: 30 November 2006Received: 15 November 2006Accepted: 30 November 2006


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.

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Autor: Misty Richards - Yoshimi Iijima - Hitomi Kondo - Tomoko Shizuno - Hiroaki Hori - Kunimasa Arima - Osamu Saitoh - Hiroshi K


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