title: Association between PNPO and schizophrenia in the Japanese population.
abstract: Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically-active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population.
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Song
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Iga
authors.forename: Sumiko
authors.initials: S
authors.lastname: Shibuya-Tayoshi
authors.forename: Masahito
authors.initials: M
authors.lastname: Nakataki
authors.forename: Shin'Ya
authors.initials: S
authors.lastname: Tayoshi
authors.forename: Ken
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Satsuki
authors.initials: S
authors.lastname: Sumitani
authors.forename: Tomohito
authors.initials: T
authors.lastname: Tomotake
authors.forename: Tomohito
authors.initials: T
authors.lastname: Tada
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Itakura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011734:Pyridoxaminephosphate Oxidase / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D018377:Neurotransmitter Agents; D011734:Pyridoxaminephosphate Oxidase