Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia

T. Suzuki, Nakao Iwata, Y. Kitamura, T. Kitajima, Y. Yamanouchi, M. Ikeda, T. Nishiyama, N. Kamatani, N. Ozaki

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The serotonin 5-HT4 receptor (5-HT4) 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-HT4 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.

Original languageEnglish
Pages (from-to)7-13
Number of pages7
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume121 B
Issue number1
Publication statusPublished - 15-08-2003

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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