title: Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Iwata
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Kitajima
authors.forename: Y
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Nishiyama
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: N
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D004252:DNA Mutational Analysis; D006239:Haplotypes; D006801:Humans; D007564:Japan; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011985:Receptors, Serotonin / Q000235:genetics*; D044422:Receptors, Serotonin, 5-HT4; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4