Association analysis of schizophrenomimetic- and D-serine-inducible genes in bipolar disorder and schizophrenia.

N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体介导的神经传递功能减退已被假设为精神分裂症的病理生理基础。在谷氨酸存在下，NMDA受体活性受甘氨酸和D-丝氨酸调节。在这项研究中，我们研究了PAPST 1（3 '-磷酸腺苷5'-磷酸硫酸转运蛋白1）在精神分裂症和双相情感障碍中的相关性，（1）因为PAPST 1是大鼠dsm-1的人类直系同源物，D-serine modulator-1调节D-丝氨酸转运，（2）因为情感障碍和精神分裂症之间存在遗传重叠。在病例对照研究中，三个多态性，rs 575034，rs 1875324和rs 3832441，显示与双相情感障碍显著相关（等位基因相关性，分别为p=.0074，p=.0075和p=.0451）。SNP（rs3832441）的基因型频率的检验即使在多重检验的Bonferroni校正（α =0.0071）之后仍然是显著的。从这三个SNPs构建的单倍型也与双相情感障碍相关。然而，在以家族为基础的关联分析中，未发现与白人双相情感障碍三人组的关联。本研究提示PAPST 1基因的SNPs可能与双相情感障碍的遗传风险有关。

Hypofunction of the N-methyl-D-aspartate (NMDA) type glutamate receptor-mediated neurotransmission has been hypothesized to underlie the pathophysiology of schizophrenia. In the presence of glutamte, NMDA receptor activity is modulated by glycine and D-serine. In this study, we examined the association of PAPST1 (3'-Phosphoadenosine 5'-Phosphosulfate Transporter 1) in schizophrenia and bipolar disorder, (1) because PAPST1 is the human ortholog of the rat dsm-1, D-serine modulator-1, which modulate the D-serine transport, and (2) because of the suggestion of a genetic overlap between affective disorders and schizophrenia. In the case-control study, three polymorphisms, rs 575034, rs 1875324 and rs 3832441, showed a significant association with bipolar disorder (allelic associations, p=.0074, p=.0075 and p=.0451, respectively). The test of genotype frequency of the SNP (rs3832441) remained significant even after Bonferroni correction (alpha=0.0071) for multiple testing. The haplotypes constructed from these three SNPs were also associated with the bipolar disorder. However, no association was found in family-based association analysis in Caucasian bipolar disorder trios. The present study suggests that SNPs in the PAPST1 may confer the genetic risk for bipolar disorder.