Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1167-72. doi: 10.1002/ajmg.b.31083.
The zinc finger DHHC domain-containing protein 8 (ZDHHC8) is located in the 22q11 microdeletion region and may contribute to the behavioral deficit associated with 22q11 deletion syndrome. Although polymorphisms of ZDHHC8 have been reported to be associated with the risk of schizophrenia, those associations are still controversial. This study was performed to validate the genetic association of ZDHHC8 polymorphisms with the risk of schizophrenia, and also to scrutinize the association with smooth pursuit eye movement (SPEM) abnormality in a Korean population. Five SNPs of ZDHHC8 were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using allele-based chi(2) analyses. Association of ZDHHC8 polymorphisms with SPEM abnormality among 166 schizophrenic patients were analyzed using multiple regressions. No ZDHHC8 polymorphisms were found to be associated with the risk of schizophrenia. However, four SNPs and one haplotype (ht4) were strongly associated with the risk of SPEM abnormality even after multiple correction (P = 0.00005-0.0007, P(corr) = 0.0001-0.002). The results of the present study provide the first evidence that ZDHHC8 on the 22q11 locus might have influence on SPEM function of schizophrenia patients in a Korean population and may provide a new clue for understanding differential effects of candidate genes in schizophrenia.
锌指 DHHC 结构域蛋白 8（ZDHHC8）位于 22q11 微缺失区域，可能与 22q11 缺失综合征相关的行为缺陷有关。虽然已经报道 ZDHHC8 的多态性与精神分裂症的风险相关，但这些关联仍然存在争议。本研究旨在验证 ZDHHC8 多态性与精神分裂症风险的遗传关联，并在韩国人群中研究其与平滑追踪眼球运动（SPEM）异常的关联。通过 TaqMan 分析对 ZDHHC8 的 5 个 SNP 进行基因分型。使用基于等位基因的 χ2 分析，在 354 例患者和 396 例对照中分析 ZDHHC8 多态性对精神分裂症风险的遗传效应。通过多元回归分析，分析了 ZDHHC8 多态性与 166 例精神分裂症患者 SPEM 异常之间的关联。未发现 ZDHHC8 多态性与精神分裂症风险相关。然而，即使在多次校正后（P=0.00005-0.0007，P(corr)=0.0001-0.002），四个 SNP 和一个单倍型（ht4）与 SPEM 异常的风险密切相关。本研究结果首次提供证据表明，位于 22q11 上的 ZDHHC8 可能对韩国人群中精神分裂症患者的 SPEM 功能有影响，并可能为理解候选基因在精神分裂症中的差异效应提供新线索。
