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      한국인 조현병 환자에서CNR1 유전자의 (AAT)n 삼핵산 반복 다형성과 안구추적운동 이상에 대한 연합 연구 = No Association between (AAT)n Repeat Polymorphisms in the Cannabinoid Receptor 1 Gene and Smooth Pursuit Eye Movement Abnormality in Korean Patients with Schizophrenia

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      https://www.riss.kr/link?id=A103049995

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      다국어 초록 (Multilingual Abstract)

      Objectives According to previous studies, the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. Some studies have linked the (AAT)n trinucleotide repeat polymorphism in CNR1 gene with the risk of schizophrenia. Meanwhile, smooth pursuit eye movement (SPEM) has been regarded as one of the most consistent endophenotypes of schizophrenia. In this study, we investigated the association between the (AAT)n trinucleotide repeats in CNR1 gene and SPEM abnormality in Korean patients with schizophrenia. Methods We measured SPEM function in 167 Korean patients with schizophrenia (84 male, 83 female) and they were divided according to SPEM function into two groups, good and poor SPEM function groups. We also investigated allele frequencies of (AAT)n repeat polymorphisms on CNR1 gene in each group. A logistic regression analysis was performed to find the association between SPEM abnormality and the number of (AAT)n trinucleotide repeats. Results The natural logarithm value of signal/noise ratio (Ln S/N ratio) of the good SPEM function group was $4.34{\pm}0.29$ and that of the poor SPEM function group was $3.21{\pm}0.70$. In total, 7 types of trinucleotide repeats were identified, each containing 7, 10, 11, 12, 13, 14, and 15 repeats, respectively. In the patients with $(AAT)7$ allele, the distributions of the good and poor SPEM function groups were 18 (11.1%) and 19 (11.0%) respectively. In the patients with $(AAT)_{10}$ allele, $(AAT)_{11}$ allele, $(AAT)_{12}$ allele, $(AAT)_{13}$ allele, $(AAT)_{14}$ allele and $(AAT)_{15}$ allele, the distributions of good and poor SPEM function groups were 13 (8.0%) and 12 (7.0%), 4 (2.5%) and 6 (3.5%), 31 (19.8%) and 35 (20.3%), 51 (31.5%) and 51 (29.7%), 36 (22.2%) and 45 (26.2%), 9 (5.6%) and 4 (2.3%) respectively. As the number of (AAT) n repeat increased, there was no aggravation of abnormality of SPEM function. Conclusions There was no significant aggravation of SPEM abnormality along with the increase of number of (AAT)n trinucleotide repeats in the CNR1 gene in Korean patients with schizophrenia.
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      Objectives According to previous studies, the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. Some studies have linked the (AAT)n trinucleotide repeat polymorphism in CNR1 gene with the risk of schizophrenia....

      Objectives According to previous studies, the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. Some studies have linked the (AAT)n trinucleotide repeat polymorphism in CNR1 gene with the risk of schizophrenia. Meanwhile, smooth pursuit eye movement (SPEM) has been regarded as one of the most consistent endophenotypes of schizophrenia. In this study, we investigated the association between the (AAT)n trinucleotide repeats in CNR1 gene and SPEM abnormality in Korean patients with schizophrenia. Methods We measured SPEM function in 167 Korean patients with schizophrenia (84 male, 83 female) and they were divided according to SPEM function into two groups, good and poor SPEM function groups. We also investigated allele frequencies of (AAT)n repeat polymorphisms on CNR1 gene in each group. A logistic regression analysis was performed to find the association between SPEM abnormality and the number of (AAT)n trinucleotide repeats. Results The natural logarithm value of signal/noise ratio (Ln S/N ratio) of the good SPEM function group was $4.34{\pm}0.29$ and that of the poor SPEM function group was $3.21{\pm}0.70$. In total, 7 types of trinucleotide repeats were identified, each containing 7, 10, 11, 12, 13, 14, and 15 repeats, respectively. In the patients with $(AAT)7$ allele, the distributions of the good and poor SPEM function groups were 18 (11.1%) and 19 (11.0%) respectively. In the patients with $(AAT)_{10}$ allele, $(AAT)_{11}$ allele, $(AAT)_{12}$ allele, $(AAT)_{13}$ allele, $(AAT)_{14}$ allele and $(AAT)_{15}$ allele, the distributions of good and poor SPEM function groups were 13 (8.0%) and 12 (7.0%), 4 (2.5%) and 6 (3.5%), 31 (19.8%) and 35 (20.3%), 51 (31.5%) and 51 (29.7%), 36 (22.2%) and 45 (26.2%), 9 (5.6%) and 4 (2.3%) respectively. As the number of (AAT) n repeat increased, there was no aggravation of abnormality of SPEM function. Conclusions There was no significant aggravation of SPEM abnormality along with the increase of number of (AAT)n trinucleotide repeats in the CNR1 gene in Korean patients with schizophrenia.

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      참고문헌 (Reference)

      1 김지원, "한국인에서 조현병과 Cannabinoid Receptor 1 유전자의 삼핵산 반복서열의 연합에 대한 연구" 대한생물정신의학회 21 (21): 99-106, 2014

      2 이창희, "한국인에서 정신분열병환자의 안구추적운동 이상과 Dystrobrevin Binding Protein 1 (DTNBP1) 유전자의 SNP A(T>A)와 P1763(A>C) 다형성의 연합에 대한 연구" 대한생물정신의학회 13 (13): 275-284, 2006

      3 장호준, "한국인 정신분열병 환자의 안구추적운동 이상과 COMT 유전자의 Val108/158Met 다형성의 연합 연구" 대한생물정신의학회 15 (15): 288-296, 2008

      4 Almeida B, "Trinucleotide repeats: a structural perspective" 4 : 76-, 2013

      5 Gagnon D, "Transcranial magnetic stimulation of frontal oculomotor regions during smooth pursuit" 26 : 458-466, 2006

      6 D’Souza DC, "The psychotomimetic effects of intravenous delta-9-tetra hydrocannabinol in healthy individuals: implications for psychosis" 29 : 1558-1572, 2004

      7 Skosnik PD, "The effect of chronic cannabinoids on broadband EEG neural oscillations in humans" 37 : 2184-2193, 2012

      8 Krauzlis RJ, "The control of voluntary eye movements: new perspectives" 11 : 124-137, 2005

      9 Cuthbert BN, "The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology" 13 : 28-35, 2014

      10 Matsuda LA, "Structure of a cannabinoid receptor and functional expression of the cloned cDNA" 346 : 561-564, 1990

      1 김지원, "한국인에서 조현병과 Cannabinoid Receptor 1 유전자의 삼핵산 반복서열의 연합에 대한 연구" 대한생물정신의학회 21 (21): 99-106, 2014

      2 이창희, "한국인에서 정신분열병환자의 안구추적운동 이상과 Dystrobrevin Binding Protein 1 (DTNBP1) 유전자의 SNP A(T>A)와 P1763(A>C) 다형성의 연합에 대한 연구" 대한생물정신의학회 13 (13): 275-284, 2006

      3 장호준, "한국인 정신분열병 환자의 안구추적운동 이상과 COMT 유전자의 Val108/158Met 다형성의 연합 연구" 대한생물정신의학회 15 (15): 288-296, 2008

      4 Almeida B, "Trinucleotide repeats: a structural perspective" 4 : 76-, 2013

      5 Gagnon D, "Transcranial magnetic stimulation of frontal oculomotor regions during smooth pursuit" 26 : 458-466, 2006

      6 D’Souza DC, "The psychotomimetic effects of intravenous delta-9-tetra hydrocannabinol in healthy individuals: implications for psychosis" 29 : 1558-1572, 2004

      7 Skosnik PD, "The effect of chronic cannabinoids on broadband EEG neural oscillations in humans" 37 : 2184-2193, 2012

      8 Krauzlis RJ, "The control of voluntary eye movements: new perspectives" 11 : 124-137, 2005

      9 Cuthbert BN, "The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology" 13 : 28-35, 2014

      10 Matsuda LA, "Structure of a cannabinoid receptor and functional expression of the cloned cDNA" 346 : 561-564, 1990

      11 Edwards CR, "Sensory gating impairments in heavy cannabis users are asso ciated with altered neural oscillations" 123 : 894-904, 2009

      12 Zammit S, "Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study" 325 : 1199-, 2002

      13 Fakhoury M, "Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia" 15-, 2016

      14 La Spada AR, "Repeat expansion disease: progress and puzzles in disease pathogenesis" 11 : 247-258, 2010

      15 Doherty JL, "Recent genomic advances in schizophrenia" 81 : 103-109, 2012

      16 Wong DF, "Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR" 52 : 1505-1513, 2010

      17 Johns A, "Psychiatric effects of cannabis" 178 : 116-122, 2001

      18 Henquet C, "Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people" 330 : 11-, 2005

      19 Nagel M, "Parametric modulation of cortical activation during smooth pursuit with and without target blanking. an fMRI study" 29 : 1319-1325, 2006

      20 Lencer R, "Neurophysiology and neuroanatomy of smooth pursuit in humans" 68 : 219-228, 2008

      21 Singer W, "Neuronal synchrony: a versatile code for the definition of relations?" 24 : 49-65, 1999

      22 Pasaje CF, "Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population" 10 : 828-833, 2011

      23 Van Essen DC, "Neural mechanisms of form and motion processing in the primate visual system" 13 : 1-10, 1994

      24 Munro S, "Molecular characterization of a peripheral receptor for cannabinoids" 365 : 61-65, 1993

      25 Ono S Das VE, "Modeling of smooth pursuit-related neuronal responses in the DLPN and NRTP of the rhesus macaque" 93 : 108-116, 2005

      26 McMurray CT, "Mechanisms of trinucleotide repeat instability during human development" 11 : 786-799, 2010

      27 Halikas JA, "Marihuana use and psychiatric illness" 27 : 162-165, 1972

      28 Annese J, "Localization of the human cortical visual area MT based on computer aided histological analysis" 15 : 1044-1053, 2005

      29 Kim JH, "Lack of associations of neuregulin 1 variations with schizophrenia and smooth pursuit eye movement abnormality in a Korean population" 46 : 476-482, 2012

      30 Skosnik PD, "It’s All in the Rhythm:The role of cannabinoids in neural oscillations and psychosis" 79 : 568-577, 2016

      31 Devane WA, "Isolation and structure of a brain constituent that binds to the cannabinoid receptor" 258 : 1946-1949, 1992

      32 Vigano D, "Involvement of the endocannabinoid system in phencyclidineinduced cognitive deficits modelling schizophrenia" 12 : 599-614, 2009

      33 Dawson E, "Genetic association between alleles of pancreatic phospholipase A2gene and bipolar affective disorder" 5 : 177-180, 1995

      34 Bae JS, "Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population" 24 : 225-229, 2014

      35 Pazos MR, "Functional neuroanatomy of the endocannabinoid system" 81 : 239-247, 2005

      36 Woo SI, "Eye tracking abnormality in schizophrenic inpatients" 18 : 100-108, 1993

      37 Jung CY, "Eye tracking abnormality in schizophrenia:follow up study after 4 months" 34 : 369-377, 1995

      38 Rais M, "Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients" 165 : 490-496, 2008

      39 Morrison PD, "Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms" 36 : 827-836, 2011

      40 Lencer R, "Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study" 19 : 1430-1436, 2004

      41 Potvin S, "Contradictory cognitive capacities among substance-abusing patients with schizophrenia: a meta-analysis" 100 : 242-251, 2008

      42 Brookes MJ, "Changes in brain network activity during working memory tasks: a magnetoencephalography study" 55 : 1804-1815, 2011

      43 Spencer DJ, "Cannabis-induced psychosis" 6 : 323-326, 1971

      44 Arseneault L, "Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study" 325 : 1212-1213, 2002

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      46 Andréasson S, "Cannabis and schizophrenia. A longitudinal study of Swedish conscripts" 2 : 1483-1486, 1987

      47 Chavarría-Siles I, "Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia" 147 : 279-284, 2008

      48 Ujike H, "CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia" 7 : 515-518, 2002

      49 Roche M, "Brain CB2 Receptors: Implications for Neuropsychiatric Disorders" 3 : 2517-2553, 2010

      50 Tsai SJ, "Association study of a cannabinoid receptor gene (CNR1) polymorphism and schizophrenia" 10 : 149-151, 2000

      51 Shin HD, "Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality" 153B : 1167-1172, 2010

      52 Cheong HS, "Association of RANBP1 haplotype with smooth pursuit eye movement abnormality" 156B : 67-71, 2011

      53 Lee YJ, "Association analysis between the G72/G30 single nucleotide polymorphisms (rs947267 and rs77829) and smooth pursuit eye movement (SPEM)abnormality of patients with schizophrenia in Korean population" 13 : 42-49, 2010

      54 Braun DI, "Anticipatory smooth eye movements and predictive pursuit after unilateral lesions in human brain" 110 : 111-116, 1996

      55 Leweke FM, "Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use" 94 : 29-36, 2007

      56 Koethe D, "Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis" 194 : 371-372, 2009

      57 Karayiorgou M, "A turning point in schizophrenia genetics" 19 : 967-979, 1997

      58 Sugiura T, "2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain" 215 : 89-97, 1995

      59 Martínez-Gras I, "(AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population" 256 : 437-441, 2006

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