Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality

Abstract

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.

Association of RANBP1 haplotype with smooth pursuit eye movement abnormality

“…In a previous study [Liu et al, 2002], a RANBP1 polymorphism (rs175163) was associated with schizophrenia vulnerability in non-22q11 deleted individuals. Our previous study also showed that ZDHHC8 SNPs, a nearby (4 kb) gene of RANBP1 were associated with SPEM abnormality in Korean schizophrenia patients [Shin et al, 2010]. Based on these previous studies about schizophrenia and SPEM abnormality, it is hypothesized that RANBP1 plays an important role in the development of schizophrenia.…”

“…The different ethnicity may be a major factor responsible for the discrepancy between the two study populations. In our previous reports about the association of COMT and ZDHHC8 with SPEM abnormality in schizophrenia patients, only ZDHHC8 polymorphisms showed strong association with SPEM abnormality in schizophrenia group [Park et al, 2009;Shin et al, 2010]. To further understand the genetic effects of the nearby gene upon SPEM abnormality in schizophrenia, we carried out an association analysis between RANBP1 and SPEM abnormality among Korean schizophrenic patients.…”

“…Previously many genetic studies were performed focusing on the association of schizophrenia with genes (COMT, HTF9C, PRODH, RANBP1, SULT4A1, and ZDHHC8) at the microdeletion locus of 22q11 [Liu et al, 2002[Liu et al, , 2007Mukai et al, 2004;Kempf et al, 2008;Meltzer et al, 2008;Park et al, 2009;Coman et al, 2010;Shin et al, 2010]. Among these previous studies, an intronic SNP, rs175163 of RANBP1 was shown to be associated with schizophrenia susceptibility in European population [Liu et al, 2002].…”

“…RANBP1 is found in complexes with RAN and transport factors [Plafker and Macara, 2002], and it may contribute to the modulation of the assembly and disassembly of these complexes [Chi et al, 1996;Kehlenbach et al, 1999]. RANBP1 is located in the microdeleted region of 22q11 locus, the deletion of which causes the Velo-cardio-facial syndrome (VCFS) characterized by high rates of schizophrenia [Murphy, 2002], and many studies have focused on the associations of the genes on the microdeletion locus of 22q11 with VCFS, and especially with schizophrenia [Badner and Gershon, 2002;Lewis et al, 2003;Mukai et al, 2004;Liu et al, 2007;Kempf et al, 2008;Meltzer et al, 2008;Park et al, 2009;Coman et al, 2010;Shin et al, 2010]. In a previous study [Liu et al, 2002], a RANBP1 polymorphism (rs175163) was associated with schizophrenia vulnerability in non-22q11 deleted individuals.…”

“…SPEM disturbance is reportedly found in approximately 40-80% of patients of schizophrenia and <10% of healthy control subjects [Holzman, 2000;Rybakowski et al, 2002]. However, the genetic origin for SPEM abnormality has been poorly understood and only a few researches such as the association studies with COMT and ZDHHC8 polymorphisms had been performed [Park et al, 2009;Vorstman et al, 2009;Shin et al, 2010].…”