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한국인 주의력결핍-과잉행동장애 아동의 세로토닌 수송체 유전자 다형성

The Serotonin Transporter Gene Polymorphism in Korean Attention-Deficit/Hyperactivity Disorder Children

김재원|유희정|김붕년|박태원|손정우|정운선|황준원|조대연|조수철
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2009.02|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제16권 제1호|pp. 25-36

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키워드

Attention-deficit/hyperactivity disorder주의력결핍-과잉행동장애․세로토닌 운반체 유전자·환자-대조군 유전연구·가족기반 유전연구serotonin transporter genecase-control analysisfamily-based association study
주제분류정신과학

초록

연구목표: 본 연구에서는 세로토닌 운반체(5-HTTLPR)의 l/s 대립유전자 다형성과 한국인 주의력결핍-과잉행동장애 환아와의 연관에 대해 알아보고자 하였다. 연구내용: Kiddie-Schedule for Affective Disorders and Schizophrenia -Present and Lifetime Version-Korean Version(K-SADS-PL-K)을 통해 주의력결핍-과잉행동장애로 진단된 189명의 환아와 환아의 부모 및 정상 대조군 아동 150명에서 혈액을 채취한 뒤 유전자를 추출했으며 유전자 분석을 실시하였다. 이를 통해 우선 환자-대조군 연합 연구를 주의력결핍-과잉행동장애 환아와 정상 대조군 간에 실시하였으며, 또한 환아 및 환아의 부모를 대상으로 가족기반 연구인 transmission/disequilibrium test(TDT)를 실시하였다(number of trio=113). 또한, 주의력결핍-과잉행동장애 환아군에서 l/s 유전자형에 따라 환아들의 임상 척도 결과 및 신경심리검사 결과를 분석하였다. 연구결과: 환자-대조군 연구에서 5-HTTLPR의 l/s 유전자 다형성에서는 여러 조건에서도 모두 유의한 차이를 보이지 않았다. 가족 기반 연합연구에서도 환아 가족 전체에서는 l 또는 s 대립유전자의 선택적 전달을 관찰할 수 없었다. 그러나, 비록 적은 숫자이긴 하나 주의력결핍-과잉행동장애의 주의력 결핍형 환아 가족 23 trio에서는 5-HTTLPR의 l 대립유전자의 선택적 가족내 전달이 통계적으로 유의하였다(χ2=4.57, p=.032). 환자군에서 l/s 유전형에 따른 임상 척도 결과 및 신경심리검사 결과를 분석하였을 때는 l/l 형에서 자극 추구성이 유의하게 낮았고(F=3.15, p=.047) 자기 초월성-영성이 유의하게 높았다(F=4.25, p=.017). 결론: 본 연구 결과는 한국인 주의력결핍-과잉행동장애 아동과 5-HTTLPR 유전자 다형성간에 유의한 연관이 없음을 시사한다.

Abstract

Objective : The aim of this study was to investigate the association between Korean ADHD patients and the l/s polymorphism of serotonin transporter(5-HTTLPR). Materials and Method : The study sample consisted of 189 Korean ADHD children diagnosed by Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version(K-SADS-PL), both parents of ADHD children, and 150 normal children. DNA were extracted from the blood of all samples, and genotyping was done. Based on the allele and genotype information, not only the case-control analysis between ADHD and normal children but also the family-based association test among ADHD children and their parents. Transmission disequilibrium test(TDT) were performed for family-based associated test(number of trio=113). The results of the clinical rating and neuropsychological tests were compared according to the l/s genotype of ADHD children. Results : In case-control analysis, there were no statistically significant difference of l/s gene polymorphism between ADHD and normal children in various kinds of analysis condition. In family-based association study, TDT failed to detect linkage disequilibrium between l/s gene polymorphism and ADHD in whole ADHD families. However, in the families of ADHD inattentive type only(number of trio=23), l allele was transmitted more preferentially in the proband with ADHD even if the number of families was small(χ2=4.57, p=.032). In the analysis of the results from the clinical scales and neuropsychological tests in ADHD children, the score of the Novelty-Seeking of ADHD children with l/l genotype was significantly lower than with the other genotypes(F=3.15, p=.047), and that of Self Transcendence was significantly higher(F=4.25, p=.017). Conclusions : The results of this study suggest there were no significant genetic association between the 5-HTTLPR gene polymorphism and Korean ADHD.

참고문헌 (47)

  1. Biderman J, "Family-genetic and psychosocial risk factors in DSM-III attention deficit disorder", J Am Acad Child Adolesc Psychiatry, 29, pp.526~533 (1990)
  2. Biederman J, "High risk for attention deficit disorder among children of parents with childhood onset of the disorder: a pilot study", Am J Psychiatry, 152, pp.431~435 (1995)
  3. Mahler BS, "Segregation analysis of attention deficit hyperactivity disorder", Am J Med Genet, 88, pp.71~78 (1999)
  4. Gjone H, "Genetic influence on parent reported attention related problems in a Norweigan general population twin study", J Am Acad Child Adolesc Psychiatry, 35, pp.588~595 (1996)
  5. Levy F, "Attention deficit hyperactivity disorder: a category or a continum? genetic analysis of a large-scale twin study", J Am Acad Child Adolesc Psychiatry, 36, pp.737~744 (1997)
  6. Rhee SH, "Sex differences in genetic and environmental influences on DSM-III-R attention deficit hyperactivity disorder", J Abnorm Psychol, 108, pp.24~41 (1999)
  7. Alberts-Corush J, "Attention and impulsivity characteristics of the biological and adoptive parents of hyperactive and normal control children", Am J Orthopsychiatry, 56, pp.413~423 (1986)
  8. Sprich S, "Adoptive and biological families of children and adolescents with ADHD", J Am Acad Child Adoles Psychiatry, 39, pp.1432~1437 (2000)
  9. Merette C, "Interpreting nonsignificant outcomes of heterogenecity tests in gene mapping", Am J Hum Genet, 49, pp.1381~1384 (1991)
  10. Purcell S, "Parental phenotypes in family-based association analysis", Am J Hum Genet, 76, pp.249~259 (2005)
  11. Spierman, RS, "Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM)", Am J Hum Genet, 52, pp.506~516 (1993)
  12. Halperin JM, "Serotonin, aggression, and parental psychopathology in children with attention-deficit hyperactivity disorder", J Am Acad Child Adolesc Psychiatry, 36, pp.1391~1398 (1997)
  13. Halperin JM, "Age-related changes in the association between serotonergic function and aggression in boys with ADHD", Biol Psychiatry, 41, pp.682~689 (1997)
  14. Gainetdinov RR, "Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity", Science, 28, pp.397~401 (1999)
  15. Quist JF, "Genetics of childhood disorders XXIII. ADHD, Part 7: the serotonin system", J Am Acad Child Adolesc Psychiatry, 40, pp.253~256 (2001)
  16. Lesch KP, "Greenberg BD, Petri S, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region", Science, 274, pp.1527~1531 (1996)
  17. Manor I, "Family-based association study of the serotonin transporter promotor polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder", Am J med genet, 105, pp.91~95 (2001)
  18. Zoroglu SS, "Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder", Neuropsychobiology, 45, pp.176~181 (2002)
  19. Seeger G, "Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders", Mole Psychiatry, 6, pp.235~238 (2001)
  20. Kent L, "Evidence that variation at the serotonin transporter gene influence susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis", Molecular Psychiatry, 7, pp.908~912 (2002)
  21. Langley K, "No evidence of association of two 5-HT transporter gene polymorphisms and with neuropsychological test performance of children with ADHD", Am J Psychiatry, 161, pp.133~138 (2003)
  22. Banerjee E, "A family-based study of indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (sTin2) polymorphism and attention deficit hyperactivity disorder", Am J Med Genet B(Neuropsychiatr Genet), 139, pp.361~366 (2006)
  23. Kim SJ, "Family-based association study of serotonin transporter gene polymorphisms in Korean ADHD trios", Am J Med Genet B (Neuropsychiatr genet), 139, pp.14~18 (2005)
  24. American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders. 4th ed" (1994), American Psychiatric Press
  25. 소유경, "한국어판 부모, 교사 ADHD 평가 척도의 신뢰도와 타당도 연구", 신경정신의학, 41(2) (2002), 대한신경정신의학회
  26. Sattler JM, "Assessment of Children's Intelligence" (1974), WB Saunders Company
  27. Kaufman J, "Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Life Time Version (K-SADS-PL): initial reliability and validity data", J Am Acad Child Adolesc Psychiatry, 36, pp.980~988 (1997)
  28. 김영신, "The Reliability and Validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version (K-SADS-PL-K)", Yonsei Medical Journal, 45(1), pp.81~89 (2004), 연세대학교의과대학
  29. DuPaul GJ, "Parent and teacher ratings of ADHD symptoms: psychometric properties in an community-based sample", J Clin Child Psychol, 20, pp.245~253 (1991)
  30. Shin MS, "A study of the development and standarization of ADHD diagnostic system", Korean J Child Adol Psychiatr, 11, pp.91~99 (2000)
  31. 4-18 and 1991 Profile, "Manual for the Child Behavior Checklist", pp.1991, Achenbach TM
  32. 오경자, "아동 청소년 행동평가척도" (1997), 중앙적성출판사
  33. Cloninger CR, "The Temperament and Character Inventory (TCI): A Guide to Its Development and Use" (1994), Washington University
  34. Luby JL, "The Junior Temperament and Character Inventory: preliminary validation of a child self-report measure", Psychol Rep, 84, pp.1127~1138 (1999)
  35. Ryoo IK, "The reliability and validity of the Junior Temperament and Character Inventory", Comp Psychiatry, 45, pp.121~128 (2004)
  36. Ha JH, "The reliability and validity of the Korean version of Junior Temperament and Character Inventory", Kor J Psychopathol, 14, pp.3~10 (2005)
  37. Mann JJ, "A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide", Arch Gen Psychiatry, 57, pp.729~738 (2000)
  38. McGee R, "A comparison of 13-year-old boys with attention deficit and", or reading disorder on neuropsychological measures, 1989, pp.17, 37~53
  39. Faraone S, "Familial subtypes of attention deficit hyperactivity disorder: a 4-year follow-up study of children from antisocial-ADHD families", J Child Psychol Psychiatry, 39, pp.1045~1053 (1998)
  40. Roman T, "Is the alpha-2A adrenergic receptor gene(ADRA2A) associated with attention-deficit", hyperactivity disorder?, 2003, pp.120, 116~120
  41. Li J, "Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects", Am J Med Genet B (Neuropsychiatr Genet), 132, pp.59~63 (2005)
  42. Wang B, "Possible association of the alpha-2A adrenergic receptor gene(ADRA2A) with symptoms of attention-deficit", hyperactivity disorder, pp.141, 130~134
  43. Retz W, "Association of serotonin transporter promotor gene polymorphism with violence: relation with personality disorders, impulsivity, and childhood ADHD psychopathology", Behav Sci Law, 22, pp.415~425 (2004)
  44. Cadoret RJ, "Associations of the serotonin transporter promotor polymorphism with aggressivity, attention deficit, and conduct disorder in an adoptee population", Comp Psychiatry, 44, pp.88~101 (2003)
  45. Vitello B, "Pharmacologic treatment of children and adolescent with attention deficit hyperactivity disorder. in: Handbook of Child and Adolescent Psychopharmacology", pp.166~ (2006), Informa Healthcare
  46. Wang D, "Sample sizes for the transmission disequilibrium tests: TDT, S-TDT and 1-TDT", Commun Stat Theory M, 29, pp.1129~1142 (2000)
  47. Doyle AE, "Attention-deficit", hyperactivity disorder endophenotypes, 2005, pp.57, 1324~1335

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