Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
342006 | Schizophrenia Research | 2007 | 7 Pages |
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.