Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality

Abstract

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using v 2 analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (P corr ¼ 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Association of RANBP1 haplotype with smooth pursuit eye movement abnormality

“…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].…”

Schizophrenia and Infections: The Eyes Have It

“…By contrast, multiple studies have assessed eye tracking in the first-degree relatives and viewed eye tracking as a marker of genetic vulnerability. 32,33 Specific genes, such as RGS4 and the catechol-O-methyltransferase (COMT) gene, have been suggested as genetic links between schizophrenia and eye tracking, 34,35 but no gene or chromosomal region has been conclusively implicated. Specific genetic defects have also been proposed to explain the occurrence of strabismus in schizophrenia 36,37 and the protective effect of congenital cortical blindness.…”

Correlations between the COMT gene rs4680 polymorphism and susceptibility to ovarian cancer

“…The catechol-O-methyltransferase (COMT) gene is located on chromosome 22q11.2 and consists of six exons, with exons 1 and 2 being noncoding (Park et al, 2009). The rs4680 polymorphism is a G-to-A transition at codon 158 in exon 4 that leads to a substitution of methionine for valine; this results in a thermolabile enzyme with reduced activity (Lachman et al, 1996).…”