Association Study of Val158Met Polymorphism of Catechol-O-Methyltransferase Gene and Cognitive Markers in Schizophrenia / 신경정신의학

OBJECTIVES: Catechol-O-methyltransferase (COMT) gene has been identified as a positional and functional candidate gene of schizophrenia. Although specific mechanism of increasing schizophrenia susceptibility by this gene has not been well described yet, recent studies suggest that the valine allele of COMT Val158Met polymorphism may contribute to cognitive decline in schizophrenia. The present study investigated the association between this polymorphism of COMT gene and cognitive markers related to schizophrenia in both schizophrenia patients and normal controls. METHODS: The subjects were 78 patients with schizophrenia diagnosed by DSM-IV and 97 normal controls. Comprehensive neurocognitive tests for which performance deficits have been reported in schizophrenia were administered. Genotyping for COMT Val158Met polymorphism was done with SNapShot method. Association analyses between genotype and cognitive functions were performed using ANCOVA and MANCOVA. RESULTS: In the comparison of allele frequencies between patient and control groups, no significant association between the polymorphism and schizophrenia was observed. Significant differences of cognitive performance among genotype groups were not identified in control group. This trend was also observed in the patient group. In the combined analysis of both patient and control groups, there was no significant genotype or genotype-by group effect on any cognitive function measure. CONCLUSION: These findings do not support a major role of COMT gene in the regulation of the cognitive processes of schizophrenia.

No Evidence for Linkage of Chromosome 6p24-22, The Locus of Dysbindin Gene, to Schizophrenia in Korean Families / 신경정신의학

OBJECTIVES: Chromosome 6p24-22 has been identified as a disease locus with a high probability for schizophrenia based on several genomewide linkage scans with Caucasian families. The recent association studies suggest that the dysbindin gene located at chromosome 6p22.3 may be a candidate gene of schizophrenia. The purpose of this study was to investigate the linkage of chromosome 6p24.3-22.3 locus to schizophrenia in Korean families. METHODS: We recruited one hundred fifty-seven family members from forty-six multiplex schizophrenia families. One hundred three of them were affected individuals. four microsatellite markers with 4.8 cM intervals on 6p24.3-22.3 were genotyped. Nonparametric linkage analysis was performed by evaluating the levels of allele sharing between the affected relative pairs. RESULTS: In the single point analysis, no markers on chromosome 6p24.3-22.3 locus showed statistical evidence for linkage. Significant evidence for linkage was not found in the multi-point analysis. CONCLUSION: These results do not support the previous evidence from Caucasian families for a locus predisposing to schizophrenia at 6p24.3-22.3, the locus of dysbindin gene. We conclude that if there is a susceptibility locus for schizophrenia in this region then its effect size is so small as to render our study insufficiently powerful to detect it and schizophrenia susceptibility loci in Korean families likey have different ethnicity-specific effects from Caucasian families.

Association of Genetic Variations within 5' end of Neuregulin 1 with Schizophrenia in Korean Population / 신경정신의학

OBJECTIVES: The authors recently found a suggestive evidence of linkage of chromosome 8p21-12 to schizophrenia in Korean multiplex families. Neuregulin 1 (NRG1) was identified in this locus as a positional and functional candidate gene for schizophrenia, through several independent studies with European and Chinese populations. The purpose of this study is to determine whether NRG1 is associated with schizophrenia in Korean population. METHODS: Three SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177) and two microsatellites markers (478B14-848, 420M9-1395) located at the 5' end of NRG1 were genotyped for 242 unrelated schizophrenia patients and the same number of normal controls. Genetic association was tested by chi2-test (df=1). Not only for the whole patients group but also for a subgroup of patients with auditory hallucination. This subtype showed stronger linkage with chromosome 8p12 in the prior study of the authors with multiplex families. RESULTS: G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with auditory hallucination compared to the control group (p=0.03, OR=1.76). We also found that 3 SNPs haplotype TTC (p=0.04, OR=0.58) and five markers haplotype TTC53 (p=0.01, OR=0.49) were associated with schziophrenia with a protective effect. Three SNPs haplotype CGT which is a part of the at-risk haplotype of the Icelandic schizophrenia families was found in excess in the patients group but no significant association was observed. CONCLUSION: NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium with a causal locus of this illness.