title: Association study of sepiapterin reductase gene promoter polymorphisms with schizophrenia in a Han Chinese population.
abstract: Sepiapterin reductase participates in the biosynthesis of tetrahydrobiopterin, which plays very important roles in the pathogenesis of schizophrenia via dysregulation of neurotransmitter systems. Here, two single nucleotide polymorphisms (rs1876487 and rs2421095) in the promoter region of SPR were genotyped in 941 schizophrenic patients and 944 controls in a Han Chinese population using the SNaPshot technique. No significant differences were found in the distribution of alleles or genotypes of the two single nucleotide polymorphisms (SNPs) between schizophrenic patients and controls (all P>0.05). Likewise, no haplotype was found to be associated with schizophrenia. However, sex-stratified analysis revealed that the frequencies of the A allele of rs1876487 and the A-A (rs2421095-rs1876487) haplotype were all significantly different between schizophrenia and controls in females (P=0.040 and P=0.033, respectively), but not in males. Additionally, luciferase reporter gene assays revealed that the A-A haplotype had significantly higher SPR transcriptional activity compared with the A-C haplotype in SH-SY5Y cells. Our data indicate that the two SNPs do not influence the risk of schizophrenia when using the total sample, but the A allele of rs1876487 and the A-A haplotype may contribute to protective roles for schizophrenia in females.
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Jiawu
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Guoda
authors.initials: G
authors.lastname: Ma
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Mai
authors.affiliation: Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Juda
authors.initials: J
authors.lastname: Lin
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
keywords: Han Chinese population; polymorphisms; schizophrenia; sepiapterin reductase; transcriptional activity