Choline Acetyltransferase 유전자 다형성이 경도인지손상 발현에 미치는 영향

The Impact of Choline Acetyltransferase Polymorphism on the Expression of Mild Cognitive Impairment

  • 이정재 (경북대학교병원 정신과학교실) ;
  • 박준혁 (제주대학교병원 정신과학교실) ;
  • 이석범 (단국대학교병원 정신과학교실) ;
  • 허윤석 (분당서울대학교병원 신경정신과학교실) ;
  • 김태희 (분당서울대학교병원 신경정신과학교실) ;
  • 윤종철 (경기도노인전문병원 신경정신과) ;
  • 주진형 (강원대학교병원 신경과학교실) ;
  • 이동영 (서울대학교병원 정신과학교실) ;
  • 박경운 (분당서울대학교병원 진단검사의학과학교실) ;
  • 김기웅 (분당서울대학교병원 신경정신과학교실)
  • Lee, Jung-Jae (Department of Psychiatry, Kyungpook National University Hospital) ;
  • Park, Joon-Hyuk (Department of Psychiatry, Jeju National University Hospital) ;
  • Lee, Seok-Bum (Department of Psychiatry, Dankook University Hospital) ;
  • Huh, Yoon-Seok (Department of Neuropsychiatry, Seoul National University Bundang Hospital) ;
  • Kim, Tae-Hui (Department of Neuropsychiatry, Seoul National University Bundang Hospital) ;
  • Youn, Jong-Chul (Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly) ;
  • Jhoo, Jin-Hyeong (Department of Neuropsychiatry, Kangwon National University Hospital) ;
  • Lee, Dong-Young (Department of Psychiatry, Seoul National University Hospital) ;
  • Park, Koung-Un (Department of Laboratory Medicine, Seoul National University Bundang Hospital) ;
  • Kim, Ki-Woong (Department of Neuropsychiatry, Seoul National University Bundang Hospital)
  • 투고 : 2010.10.18
  • 심사 : 2010.10.26
  • 발행 : 2010.11.30

초록

Objectives : The potential association between choline acetyltransferase(CHAT) polymorphism and the risk of mild cognitive impairment(MCI) has not been investigated in Korea. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E(APOE) polymorphism in the development of MCI in elderly Korean sample. Methods : We analyzed CHAT 2384G > A polymorphism and APOE polymorphism among 149 MCI subjects with MCI and 298 normal controls. We tested the association between MCI and CHAT A allele status using a logistic regression model. In addition, we employed generalized multifactor dimensionality reduction(GMDR) to investigate the interaction between CHAT and APOE with regard to the risk of MCI. Results : The CHAT A allele was associated with AD risk(OR = 1.59, 95% CI = 1.02-2.48, p = 0.042). No significant gene-gene interaction between CHAT and APOE was found in GMDR method(testing balanced accuracy = 0.540, p = 0.055). Conclusion : The CHAT A allele was associated with MCI risk in the Korean elderly. Its interaction with the APOE ${\varepsilon}4$ allele was not significant with regard to the development of MCI.

키워드

참고문헌

  1. Kim KW, Park JH, Kim MH, Kim MD, Kim BJ, Kim SG, et al. A nationwide survey on the prevalence of dementia and mild cognitive impairment(MCI) in South Korea. J Alzheimers Dis(in press).
  2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303-308. https://doi.org/10.1001/archneur.56.3.303
  3. Mubumbila V, Sutter A, Ptok U, Heun R, Quirin-Stricker C. Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease. Neurosci Lett 2002;333:9-12. https://doi.org/10.1016/S0304-3940(02)00955-2
  4. Kim KW, Suh YJ, Park WY, Jhoo JH, Lee DY, Youn JC, et al. Choline acetyltransferase G +4 A polymorphism confers a risk for Alzheimer's disease in concert with Apolipoprotein E epsilon4. Neurosci Lett 2004;366:182-186. https://doi.org/10.1016/j.neulet.2004.05.041
  5. Ahn Jo S, Ahn K, Kim JH, Kang BH, Kim E, Jo I, et al. ApoE-epsilon 4-dependent association of the choline acetyltransferase gene polymorphisms(2384G>A and 1882G>A) with Alzheimer's disease. Clin Chim Acta 2006;368:179-182. https://doi.org/10.1016/j.cca.2005.12.037
  6. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976;2:1403.
  7. Perry EK, Perry RH, Blessed G, Tomlinson BE. Necropsy evidence of central cholinergic deficits in senile dementia. Lancet 1977;1:189.
  8. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978;2:1457-1459. https://doi.org/10.1136/bmj.2.6150.1457
  9. Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res 1979;171:319-327. https://doi.org/10.1016/0006-8993(79)90336-6
  10. Wilcock GK, Esiri MM, Bowen DM, Smith CC. Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci 1982;57:407-417. https://doi.org/10.1016/0022-510X(82)90045-4
  11. Bierer LM, Haroutunian V, Gabriel S, Knott PJ, Carlin LS, Purohit DP, et al. Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. J Neurochem 1995;64:749-760.
  12. DeKosky ST, Ikonomovic MD, Styren SD, Beckett L, Wisniewski S, Bennett DA, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002;51:145-155. https://doi.org/10.1002/ana.10069
  13. Tang M, Rao D, Ma C, Guo Y, Han H, Ling K, et al. Evaluation of choline acetyltransferase gene polymorphism( 2384 G/A) in Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord 2008;26:9-14. https://doi.org/10.1159/000140612
  14. Park JH, Lim S, Lim JY, Han MK, Yoon IY, Kim JM, et al. An overview of the Korean longitudinal study on health and aging. Pschiatry Invest 2007;4:84-95.
  15. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-194. https://doi.org/10.1111/j.1365-2796.2004.01388.x
  16. Lee JH, Lee KU, Lee DY, Kim KW, Jhoo JH, Kim JH, et al. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet(CERAD-K): clinical and neuropsychological assessment batteries. J Gerontol B Psychol Sci Soc Sci 2002;57:P47-P53. https://doi.org/10.1093/geronb/57.1.P47
  17. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview(M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59 Suppl 20:22-33; quiz 34-57.
  18. Yoo SW, Kim YS, Noh JS, Oh KS, Kim CH, Nam KK, et al. Validity of Korean Version of the Mini-international Neuropsychiatric interview. Anxiety Mood 2006;2:50-55.
  19. Ruff RM, Light RH, Parker SB, Levin HS. Benton Controlled Oral Word Association Test: reliability and updated norms. Arch Clin Neuropsychol 1996;11:329-338. https://doi.org/10.1093/arclin/11.4.329
  20. Wechsler D. Wechsler Adult Intelligence Scale-administration and scoring manual. 3rd ed. San Antonio, TX: The Psychological Corporation;1997.
  21. Kim KW, Jhoo JH, Lee KU, Lee DY, Lee JH, Youn JY, et al. Association between apolipoprotein E polymorphism and Alzheimer's disease in Koreans. Neurosci Lett 1999;277:145-148. https://doi.org/10.1016/S0304-3940(99)00867-8
  22. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 2001;69:138-147. https://doi.org/10.1086/321276
  23. Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 2003;19:376-382. https://doi.org/10.1093/bioinformatics/btf869
  24. Harold D, Peirce T, Moskvina V, Myers A, Jones S, Hollingworth P, et al. Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease. Hum Genet 2003;113:258-267. https://doi.org/10.1007/s00439-003-0960-2
  25. Schwarz S, Eisele T, Diehl J, Muller U, Forstl H, Kurz A, et al. Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease. Neurosci Lett 2003;343:167-170. https://doi.org/10.1016/S0304-3940(03)00380-X
  26. Cook LJ, Ho LW, Wang L, Terrenoire E, Brayne C, Evans JG, et al. Candidate gene association studies of genes involved in neuronal cholinergic transmission in Alzheimer's disease suggests choline acetyltransferase as a candidate deserving further study. Am J Med Genet B Neuropsychiatr Genet 2005;132:5-8.
  27. Ozturk A, DeKosky ST, Kamboh MI. Genetic variation in the choline acetyltransferase(CHAT) gene may be associated with the risk of Alzheimer's disease. Neurobiol Aging 2006;27:1440-1444. https://doi.org/10.1016/j.neurobiolaging.2005.08.024
  28. Grunblatt E, Zehetmayer S, Bartl J, Loffler C, Wichart I, Rainer MK, et al. Genetic risk factors and markers for Alzheimer's disease and/or depression in the VITA study. J Psychiatr Res 2009;43:298-308. https://doi.org/10.1016/j.jpsychires.2008.05.008
  29. Kozak M. Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6. EMBO J 1997;16:2482-2492. https://doi.org/10.1093/emboj/16.9.2482
  30. Cohen EL, Wurtman RJ. Brain acetylcholine: increase after systemic choline administration. Life Sci 1975;16:1095-1102. https://doi.org/10.1016/0024-3205(75)90194-0
  31. Haubrich DR, Chippendale TJ. Regulation of acetylcholine synthesis in nervous tissue. Life Sci 1977;20:1465-1478. https://doi.org/10.1016/0024-3205(77)90437-4
  32. Baskin DS, Browning JL, Pirozzolo FJ, Korporaal S, Baskin JA, Appel SH. Brain choline acetyltransferase and mental function in Alzheimer disease. Arch Neurol 1999;56:1121-1123. https://doi.org/10.1001/archneur.56.9.1121
  33. Kim JM, Shin IS, Yoon JS. Apolipoprotein E among Korean Alzheimer's disease patients in community-dwelling and hospitalized elderly samples. Dement Geriatr Cogn Disord 2002;13:119-124. https://doi.org/10.1159/000048643