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Am J Med Genet B Neuropsychiatr
Genet. 2003 Aug 15;121(1):7-13. |
Association
of a haplotype in the serotonin 5-HT4 receptor gene
(HTR4) with Japanese schizophrenia.
Suzuki T, Iwata N, Kitamura Y, Kitajima
T, Yamanouchi Y, Ikeda M, Nishiyama
T, Kamatani
N, Ozaki N.
Department of Psychiatry,
The serotonin 5-HT(4) receptor (5-HT(4)) is implicated
in cognitive function, of which impairment is hypothesized as one of the core
disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which
HTR4 is located, is schizophrenia-susceptibility loci. We therefore
hypothesized that variation in the 5-HT(4) receptor
gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding
regions and introns that include the branch sites of
HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing
high-performance liquid chromatography analysis. One silent single nucleotide
polymorphism (SNP) within the coding region and six intronic
SNPs were detected. 353 + 6G > A was located in
the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare-allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to
299 controls. However, a highly significant association between schizophrenia
and haplotype A-T (OR = 0.13 [0.03-0.58]) was
detected. These findings suggest that haplotype A-T
itself may inhibit the occurrence of schizophrenia, or that another
susceptible genetic variants may exist within linkage disequilibrium.
Copyright 2003 Wiley-Liss, Inc.
PMID: 12898568 [PubMed - indexed for MEDLINE]
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Mol Psychiatry. 2002;7(9):954-61. |
Association
between serotonin 4 receptor gene polymorphisms and bipolar disorder in
Japanese case-control samples and the NIMH Genetics Initiative Bipolar
Pedigrees.
Ohtsuki
T, Ishiguro H, Detera-Wadleigh SD, Toyota T, Shimizu H, Yamada K, Yoshitsugu
K, Hattori E, Yoshikawa T, Arinami
T.
Department of Medical Genetics, Institute of Basic Medical Sciences,
Possible irregularities in serotonergic
neurotransmission have been suggested as causes of a variety of neuropsychiatric diseases. We performed mutation and
association analyses of the HTR4 gene, on 5q32, encoding the serotonin 4
receptor in mood disorders and schizophrenia. Mutation analysis was performed
on the HTR4 exons and exon/intron
boundaries in 48 Japanese patients with mood disorders and 48 patients with
schizophrenia. Eight polymorphisms and four rare variants were identified. Of
these, four polymorphisms at or in close proximity to exon
d, g.83097C/T (HTR4-SVR (splice variant region) SNP1), g.83159G/A
(HTR4-SVRSNP2), g.83164 (T)9-10 (HTR4-SVRSNP3), and
g.83198A/G (HTR4-SVRSNP4), showed significant association with bipolar disorder
with odds ratios of 1.5 to 2. These polymorphisms were in linkage
disequilibrium, and only three common haplotypes were
observed. One of the haplotypes showed significant
association with bipolar disorder (P = 0.002). The genotypic and haplotypic associations with bipolar disorder were
confirmed by transmission disequilibrium test in the NIMH Genetics Initiative
Bipolar Pedigrees with ratios of transmitted to not transmitted alleles of 1.5
to 2.0 (P = 0.01). The same haplotype that showed
association with bipolar disorder was suggested to be associated with
schizophrenia in the case-control analysis (P = 0.003) but was not confirmed
when Japanese schizophrenia families were tested. The polymorphisms associated
with mood disorder were located within the region that encodes the divergent
C-terminal tails of the 5-HT(4) receptor. These
findings suggest that genomic variations in the HTR4 gene may confer
susceptibility to mood disorder.
PMID: 12399948 [PubMed - indexed for MEDLINE]
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Eur Urol. 2005 Jun;47(6):895-900. Epub 2005 Mar 3. |
Expression
of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of
their antagonists on prostate cancer cell lines.
Dizeyi N, Bjartell A, Hedlund P, Tasken KA, Gadaleanu V, Abrahamsson PA.
Department of Urology,
OBJECTIVES: Overexpression of receptors to neuroendocrine (NE) cell products has been suggested to
contribute to development of hormone-refractory prostate cancer (HRPC). In this
study, we evaluated the expression of 5-HTR2B and 5-HTR4 in HRPC, and the
effects of their antagonist on PC cell line growth. METHODS: Proteins and mRNA
expression was determined by immunohistochemistry,
western blot and RT-PCR. Growth inhibition of PC cell lines was determined in
vitro using ELISA-BrdU proliferation assay and cell
cycle was evaluated by flow cytometry. RESULTS: Immunostaining of 5-HTR2B was observed in low-grade and
high-grade tumours, PIN and BPH cells, and in
vascular endothelial cells, whereas 5-HTR4 was found predominantly in
high-grade tumours. This result was confirmed by
western blot analysis. At the mRNA level, 5-HTR4 mRNA was expressed in DU145
and LNCaP cells. Antagonists to both receptor
subtypes inhibited proliferation of PC cells in a dose-dependent manner.
CONCLUSIONS: The present result indicate that 5-HTRs
are present at various tumour stages and that
antagonists to these receptors can inhibit the proliferative
activity of androgen-independent PC cell lines.
PMID: 15925089 [PubMed - indexed for MEDLINE]