Association between PNPO and schizophrenia in the Japanese population

• Published in: Schizophrenia research Vol. 97; no. 1; pp. 264 - 270
• Main Authors: Song, Hongwei, Ueno, Shu-ichi, Numata, Shusuke, Iga, Jun-ichi, Shibuya-Tayoshi, Sumiko, Nakataki, Masahito, Tayoshi, Shin'Ya, Yamauchi, Ken, Sumitani, Satsuki, Tomotake, Tomohito, Tada, Tomohito, Tanahashi, Toshihito, Itakura, Mitsuo, Ohmori, Tetsuro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2007; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Alleles; Asian Continental Ancestry Group - genetics; Association study; Biological and medical sciences; Female; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genotype; Haplotypes; Homocysteinemia; Humans; Japan; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Neurotransmitter Agents - metabolism; PNPO; Polymorphism, Single Nucleotide - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Pyridoxaminephosphate Oxidase - genetics; Risk Factors; Schizophrenia; Schizophrenia - genetics; Vitamin B 6; Japan; Association study; PNPO; Schizophrenia; Vitamin B 6; Homocysteinemia; Micronutrient; Psychosis; Human; Vitamin; Japanese; Vitamin B6
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2007.08.004

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 B6 ) synthesis. PLP is a metabolically-active form of vitamin B6 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.