정신분열병의 인지적 표지자와 Catechol-O-Methyltransferase Val158Met 유전자 다형성의 연합연구
Association Study of Val158Met Polymorphism of Catechol-O-Methyltransferase Gene and Cognitive Markers in Schizophrenia
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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. (J Korean Neuropsychiatr Assoc 2008;47(2):126-133)
Abstract
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. (J Korean Neuropsychiatr Assoc 2008;47(2):126-133)
참고문헌 (38)
- Harrison PJ, "Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence", Mol Psychiatry, 10, pp.40~68 (2005)
- Hennah W, "Haplotype analysis and identification of genes for a complex trait: examples from schizophrenia", Ann Med, 36, pp.322~331 (2004)
- Morrow B, "Molecular definition of the 22q11 deletions in velo-cardiofacial syndrome", Am J Hum Genet, 56, pp.1391~1403 (1995)
- Pulver AE, "Psychotic illness in patients diagnosed with velo-cardiofacial syndrome and their relatives", J Nerv Ment Dis, 182, pp.476~478 (1994)
- Lachman HM, "Association of codon 108", 158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardiofacial syndrome, 1996, pp.67, 468~472
- Murphy KC, "High rates of schizophrenia in adults with velo-cardio-facial syndrome", Arch Gen Psychiatry, 56, pp.940~945 (1999)
- Lotta T, "Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme", Biochemistry, 34, pp.4202~4210 (1995)
- Egan MF, "Effect of COMT Val108", 158 Met genotype on frontal lobe function and risk for schizophrenia, 2001, pp.98, 6917~6922
- Kunugi H, "Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families", Psychiatr Genet, 7, pp.97~101 (1997)
- Daniels JK, "No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity", Am J Psychiatry, 153, pp.268~270 (1996)
- Karayiorgou M, "Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility", Biol Psychiatry, 43, pp.425~431 (1998)
- Li T, "Preferential transmission of the high activity allele of COMT in schizophrenia", Psychiatr Genet, 6, pp.131~133 (1996)
- Ohmori O, "Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics", Neurosci Lett, 243, pp.109~112 (1998)
- Chen CH, "Systematic mutation analysis of the catechol O-methyltransferase gene as a candidate gene for schizophrenia", Am J Psychiatry, 156, pp.1273~1275 (1999)
- Fan JB, "Catechol- O-methyltransferase gene Val", Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis, 2005, pp.57, 139~144
- Inada T, "Relationship between catechol-Omethyltransferase polymorphism and treatment-resistant schizophrenia", Am J Med Genet B Neuropsychiatr Genet, 120, pp.35~39 (2003)
- Yu R, "Association analysis of COMT polymorphisms and schizophrenia in a Chinese Han population: a case-control study", Am J Med Genet B Neuropsychiatr Genet, 144, pp.570~573 (2007)
- Park TW, "Association study of functional catechol-O-methyltransferase gene polymorhism in Korean schizophrenia", J Korean Neuropsychiatr Assoc, 40, pp.708~717 (2001)
- Joo EJ, "Genetic association between single nucleotide polymorphism on COMT gene and schizophrenia in Korean population", Korean J Psychopharmacol, 14, pp.172~180 (2003)
- Kim MS, "Catechol-O-methyltransferase genepolymorphism (valine", methionine) associated neither with schizophrenia nor with bipolar disorder in a Korean population, 2001, pp.40, 510~519
- Lee SG, "Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans", Hum Genet, 116, pp.319~328 (2005)
- Flint J, "The endophenotype concept in psychiatric genetics", Psychol Med, 37, pp.163~180 (2007)
- Bilder RM, "Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia", Biol Psychiatry, 52, pp.701~707 (2002)
- Joober R, "Catechol-O-methyltransferase Val-108", 158-Met gene variants associated with performance on the Wisconsin Card Sorting Test, 2002, pp.59, 662~663
- Goldberg TE, "Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia", Arch Gen Psychiatry, 60, pp.889~896 (2003)
- Ho BC, "Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow", Mol Psychiatry, 10(229), pp.287~298 (2005)
- Szöke A, "Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first-degree relatives and controls", Am J Med Genet B Neuropsychiatr Genet, 141, pp.504~512 (2006)
- Malhotra AK, "A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition", Am J Psychiatry, 159, pp.652~654 (2002)
- Bruder GE, "Gorman JM", Biol Psychiatry, 58, pp.901~907 (2005)
- Tsai SJ, "Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females", Neurosci Lett, 338, pp.123~126 (2003)
- Rosa A, "New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis", Am J Psychiatry, 161, pp.1110~1112 (2004)
- Nolan KA, "Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Val and Met alleles on cognitive stability and flexibility", Am J Psychiatry, 161, pp.359~361 (2004)
- Kaasinen V, "Age-related dopamine D2", D3 receptor loss in extrastriatal regions of the human brain, 2000, pp.21, 683~688
- de Keyser J, "The effect of aging on the D1 dopamine receptors in human frontal cortex", Brain Res, 528, pp.308~310 (1990)
- Goldman-Rakic PS, "Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys", Neuroscience, 6, pp.177~187 (1981)
- Rinne JO, "Muscarinic and dopaminergic receptors in the aging human brain", Brain Res, 404, pp.162~168 (1987)
- Suhara T, "Age-related changes in human D1 dopamine receptors measured by positron emission tomography", Psychopharmacology (Berl), 103, pp.41~45 (1991)
- Volkow ND, "Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism", Am J Psychiatry, 157, pp.75~80 (2000)