期刊
MOLECULAR PSYCHIATRY
卷 7, 期 9, 页码 954-961出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4001133
关键词
HTR4; schizophrenia; affective disorder; polymorphism; haplotype; transmission disequilibrium test; association
资金
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH046282, U01MH046274, U01MH046280] Funding Source: NIH RePORTER
- NIMH NIH HHS [U01 MH46282, U01 MH46274, U01 MH46280] Funding Source: Medline
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-HT4 receptor. These findings suggest that genomic variations in the HTR4 gene may confer susceptibility to mood disorder.
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