Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Association Analysis between (AAT)n Repeats in the Cannabinoid Receptor 1 Gene and Schizophrenia in a Korean Population

한국인에서 조현병과 Cannabinoid Receptor 1 유전자의 삼핵산 반복서열의 연합에 대한 연구

  • Kim, Ji-Won (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Roh, Yang-Ho (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Kim, Min-Jea (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Kim, Chea-Ri (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Park, Byung-Lae (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Bae, Joon Seol (Laboratory of Translational Genomics, Samsung Genome Institute, Samsung Medical Center) ;
  • Shin, Hyoung Doo (Department of Life Science, Sogang University) ;
  • Choi, Ihn-Geun (Department of Neuropsychiatry, Kangnam Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Han, Sang-Woo (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Hwang, Jaeuk (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University) ;
  • Woo, Sung-Il (Department of Psychiatry, Soonchunhyang University Seoul Hospital, College of Medicine, Soonchunhyang University)
  • 김지원 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 노양호 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 김민재 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 김채리 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 박병래 ((주)에스엔피 제네틱스 유전역학부) ;
  • 배준설 (삼성의료원 삼성유전체연구소 유전체의학연구실) ;
  • 신형두 (서강대학교 생명공학과) ;
  • 최인근 (한림대학교 의과대학 강남성심병원 정신건강의학교실) ;
  • 한상우 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 황재욱 (순천향대학교 의과대학 서울병원 정신건강의학교실) ;
  • 우성일 (순천향대학교 의과대학 서울병원 정신건강의학교실)
  • Received : 2014.06.12
  • Accepted : 2014.07.24
  • Published : 2014.08.28
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Abstract

Objectives Previous studies suggest that the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. According to linkage studies, this gene is located on chromosome 6q14-q15, which is known to harbor the schizophrenia susceptibility locus (locus 5, SCZ5, OMIM 803175). The pharmacological agent delta-9-tetrahydrocannabinol (${\Delta}$-9-THC) seems to elicit the symptoms of schizophrenia. The association between CNR1 polymorphisms and schizophrenia is actively being investigated, and some studies have linked the AAT-trinucleotide repeats in CNR1 to the onset of schizophrenia. In this study, we have investigated the association between the AAT-trinucleotide repeats in CNR1 and schizophrenia by studying schizophrenia patients and healthy individuals from Korea. Methods DNA was extracted from the blood samples of 394 control subjects and 337 patients diagnosed with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria). After polymerase chain reaction amplification, a logistic regression analysis, with age and gender as the covariates, was performed to study the variations in the AAT-repeat polymorphisms between the two groups. Results In total, 8 types of trinucleotide repeats were identified, each containing 7, 8, 10, 11, 12, 13, 14, and 15 repeats, respectively. $(AAT)_{13}$ allele was most frequently observed, with a frequency of 33.6% and 31.6% in the patient and control groups, respectively. The frequency of the other repeat alleles in the patient group (in the decreasing order) was as follows : $(AAT)_{13}$ 33.6%, $(AAT)_{14}$ 21.6%, $(AAT)_{12}$ 18.5%, and $(AAT)_{7}$ 11.1%. The frequency of the repeat alleles in the control group (in the decreasing order) was as follows : $(AAT)_{13}$ 31.6%, $(AAT)_{14}$ 24.5%, $(AAT)_{12}$ 17.2%, and $(AAT)_{7}$ 11.6%. However, there were no significant differences in the AAT-repeat polymorphisms of the CNR1 gene between the patient group and the control group. Conclusions Although our study revealed no significant association of the AAT-repeat polymorphism of the CNR1 gene with schizophrenia, it will serve as a good reference for future studies designed to examine the cannabinoid hypothesis of schizophrenia.

Keywords

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