Association between PNPO and schizophrenia in the Japanese population.
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.
Song
Hongwei
H
Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
Ueno
Shu-ichi
S
Numata
Shusuke
S
Iga
Jun-ichi
J
Shibuya-Tayoshi
Sumiko
S
Nakataki
Masahito
M
Tayoshi
Shin'Ya
S
Yamauchi
Ken
K
Sumitani
Satsuki
S
Tomotake
Tomohito
T
Tada
Tomohito
T
Tanahashi
Toshihito
T
Itakura
Mitsuo
M
Ohmori
Tetsuro
T
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*
D005819:Genetic Markers; D018377:Neurotransmitter Agents; D011734:Pyridoxaminephosphate Oxidase