Saviouk Viatcheslav, Moreau Michael P, Tereshchenko Irina V, Brzustowicz Linda M
Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.
Schizophr Res. 2007 Nov;96(1-3):100-11. doi: 10.1016/j.schres.2007.07.031. Epub 2007 Sep 4.
The synapsin 2 (Syn2) gene (3p25) is implicated in synaptogenesis, neurotransmitter release, and the localization of nitric oxide synthase to the proximity of its targets. In this study we investigated linkage and association between the Syn2 locus and schizophrenia. 37 pedigrees of Northern European ancestry from the NIMH Human Genetics Initiative collection were used. Four microsatellites and twenty SNPs were genotyped. Linkage (FASTLINK) and association (TRANSMIT, PDTPHASE) between markers and schizophrenia were evaluated. A maximum heterogeneity LOD of 1.93 was observed at marker D3S3434 with a recessive mode of inheritance. Significant results were obtained for association with schizophrenia using TRANSMIT (minimum nominal p=0.0000005) and PDTPHASE (minimum nominal p=0.014) using single marker analyses. Haplotype analysis using markers in introns 5 and 6 of Syn2 provided a single haplotype that is significantly associated with schizophrenia using TRANSMIT (nominal p<0.00000001) and PDTPHASE (nominal p=0.02). Simulation studies confirm the global significance of these results, but demonstrate that the small p-values generated by the bootstrap routine of TRANSMIT can be consistently anticonservative. Review of the literature suggests that Syn2 is likely to be involved in the etiology or pathogenesis of schizophrenia.
突触结合蛋白2（Syn2）基因（3p25）与突触形成、神经递质释放以及一氧化氮合酶在其靶标附近的定位有关。在本研究中，我们调查了Syn2基因座与精神分裂症之间的连锁和关联。使用了来自美国国立精神卫生研究所人类遗传学倡议收集的37个北欧血统的家系。对四个微卫星和二十个单核苷酸多态性进行了基因分型。评估了标记与精神分裂症之间的连锁（FASTLINK）和关联（TRANSMIT、PDTPHASE）。在标记D3S3434处观察到最大异质性对数优势比为1.93，呈隐性遗传模式。使用TRANSMIT（最小名义p = 0.0000005）和PDTPHASE（最小名义p = 0.014）进行单标记分析，获得了与精神分裂症关联的显著结果。使用Syn2第5和第6内含子中的标记进行单倍型分析，得到一个单倍型，使用TRANSMIT（名义p < 0.00000001）和PDTPHASE（名义p = 0.02）与精神分裂症显著相关。模拟研究证实了这些结果的整体显著性，但表明TRANSMIT的自展程序产生的小p值可能始终是反保守的。文献综述表明，Syn2可能参与精神分裂症的病因学或发病机制。
