본문 바로가기
KERD
논문KCI 등재

Association of the Brain-derived Neurotrophic Factor Gene and Clinical Features of Bipolar Disorder in Korea

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

초록

Objective: Brain-derived neurotrophic factor (BDNF) plays an important role in cell survival, differentiation, and cell death as well as in neural plasticity. Recent studies have suggested that BDNF is involved in the pathogenesis of bipolar disorder. The aim of this study was to investigate the association of the genetic variations of the BDNF gene with bipolar disorder in Korea. We also studied the possible association of these genetic variants with clinical features. Methods: The allelic and genotypic distributions of Val66Met polymorphism of the BDNF gene were analyzed using a polymerase chain reaction-based method in 184 bipolar patients and 214 controls. Analysis was performed to investigate an association of the Val66Met polymorphism of the BDNF gene and the clinical features in bipolar patients. Results: No significant difference was found between bipolar patients and controls in the genotype and allele frequencies for the investigated BDNF polymorphism. However, the age of onset of bipolar disorder among the Val/Val (25.57), Val/Met (30.42)and Met/Met (32.45) genotype groups were significantly different (p=0.037). Conclusion: This study suggests that Val66Met polymorphisms are unlikely to contribution to the genetic predisposition to bipolar disorder as a whole. But Val66Met polymorphism may be associated with age of onset of the disorder, further studies designed to investigate the relationship in a larger population may be warranted.

Abstract

Objective: Brain-derived neurotrophic factor (BDNF) plays an important role in cell survival, differentiation, and cell death as well as in neural plasticity. Recent studies have suggested that BDNF is involved in the pathogenesis of bipolar disorder. The aim of this study was to investigate the association of the genetic variations of the BDNF gene with bipolar disorder in Korea. We also studied the possible association of these genetic variants with clinical features. Methods: The allelic and genotypic distributions of Val66Met polymorphism of the BDNF gene were analyzed using a polymerase chain reaction-based method in 184 bipolar patients and 214 controls. Analysis was performed to investigate an association of the Val66Met polymorphism of the BDNF gene and the clinical features in bipolar patients. Results: No significant difference was found between bipolar patients and controls in the genotype and allele frequencies for the investigated BDNF polymorphism. However, the age of onset of bipolar disorder among the Val/Val (25.57), Val/Met (30.42)and Met/Met (32.45) genotype groups were significantly different (p=0.037). Conclusion: This study suggests that Val66Met polymorphisms are unlikely to contribution to the genetic predisposition to bipolar disorder as a whole. But Val66Met polymorphism may be associated with age of onset of the disorder, further studies designed to investigate the relationship in a larger population may be warranted.

참고문헌 (43)

  1. Jones KR, "Molecular cloning of a human gene that is a member of the nerve growth factor family", Proc Natl Acad Sci U S A, 87, pp.8060~8064 (1990)
  2. Hofer MM, "Brain-derived neurotrophic factor prevents neuronal death in vivo", Nature, 331, pp.261~262 (1988)
  3. Hanson IM, "The human BDNF gene maps between FSHB and HVBS1 at the boundary of 11p13-p14", Genomics, 13, pp.1331~1333 (1992)
  4. Altar CA, "Anterograde transport of brain-derived neurotrophic factor and its role in the brain", Nature, 389, pp.856~860 (1997)
  5. Bartrup JT, "BDNF enhances neuronal growth and synaptic activity in hippocampal cell cultures", Neuroreport, 8, pp.3791~3794 (1997)
  6. Huang EJ, "Neurotrophins: roles in neuronal development and function", Annu Rev Neurosci, 24, pp.677~736 (2001)
  7. Nibuya M, "Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments", J Neurosci, 15, pp.7539~7547 (1995)
  8. Chen B, "Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication", Biol Psychiatry, 50, pp.260~265 (2001)
  9. Fukumoto T, "Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain", Psychopharmacology, 158, pp.100~106 (2001)
  10. Hashimoto R, "Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity", Neuropharmacology, 43, pp.1173~1179 (2002)
  11. Shimizu E, "Alterations of serum levels of brain- derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants", Biol Psychiatry, 54, pp.70~75 (2003)
  12. Gonul AS, "Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients", Eur Arch Psychiatry Clin Neurosci, 255, pp.381~386 (2005)
  13. Karege F, "Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs", Brain Res Mol Brain Res, 136, pp.29~37 (2005)
  14. Chang YC, "Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression levels in rat frontal cortex", Neurochem Res, 34, pp.536~541 (2009)
  15. Sheline YI, "Untreated depression and hippocampal volume loss", Am J Psychiatry, 160, pp.1516~1518 (2003)
  16. Egan MF, "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function", Cell, 112, pp.257~269 (2003)
  17. Neves-Pereira M, "The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study", Am J Hum Genet, 71, pp.651~655 (2002)
  18. Sklar P, "Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus", Mol Psychiatry, 7, pp.579~593 (2002)
  19. Oswald P, "Non-replication of the brain-derived neurotrophic factor (BDNF) association in bipolar affective disorder: a Belgian patient-control study", Am J Med Genet B Neuropsychiatr Genet, 129B, pp.34~35 (2004)
  20. Skibinska M, "Association analysis of brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism in schizophrenia and bipolar affective disorder", World J Biol Psychiatry, 5, pp.215~220 (2004)
  21. Neves-Pereira M, "BDNF gene is a risk factor for schizophrenia in a Scottish population", Mol Psychiatry, 10, pp.208~212 (2005)
  22. Hong CJ, "Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior", Neuropsychobiology, 48, pp.186~189 (2003)
  23. Nakata K, "Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder", Neurosci Lett, 337, pp.17~20 (2003)
  24. Kunugi H, "No association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder in a Japanese population: a multicenter study", Biol Psychiatry, 56, pp.376~378 (2004)
  25. Kim B, "Brain-derived neurotrophic factor Val", Met polymorphism and bipolar disorder. Association of the Met allele with suicidal behavior of bipolar patients, 2008, pp.58, 97~103
  26. Green EK, "Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control study of over 3000 individuals from the UK", Br J Psychiatry, 188, pp.21~25 (2006)
  27. Mü~ller DJ, "Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study", Br J Psychiatry, 189, pp.317~323 (2006)
  28. Geller B, "Linkage disequilibrium of the brain-derived neurotrophic factor Val66Met polymorphism in children with a prepubertal and early adolescent bipolar disorder phenotype", Am J Psychiatry, 161, pp.1698~1700 (2004)
  29. Strauss J, "Association study of brain-derived neurotrophic factor in adults with a history of childhood onset mood disorder", Am J Med Genet B Neuropsychiatr Genet, 131B, pp.16~19 (2004)
  30. American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders, 4th ed" (1994), American Psychiatric Association
  31. Carlson GA, "Bipolar affective disorders in childhood and adolescence, In Affective disorder in childhood and adolescence: An update", pp.61~83 (1983), Spectrum Publication
  32. Rybakowski JK, "Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients", Bipolar Disord, 5, pp.468~472 (2003)
  33. Tang J, "Association of the brain-derived neurotrophic factor gene and bipolar disorder with early age of onset in mainland China", Neurosci Lett, 433, pp.98~102 (2008)
  34. Pandey GN, "Brainderived neurotrophic factor gene expression in pediatric bipolar disorder: effects of treatment and clinical response", J Am Acad Child Adolesc Psychiatry, 47, pp.1077~1085 (2008)
  35. Hall D, "Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessivecompulsive disorder", Am J Hum Genet, 73, pp.370~376 (2003)
  36. Ribasé~s M, "Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type", Mol Psychiatry, 8, pp.745~751 (2003)
  37. Rosa A, "The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study", Am J Med Genet B Neuropsychiatr Genet, 141B, pp.135~138 (2006)
  38. Numata S, "Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms", Neurosci Lett, 401, pp.1~5 (2006)
  39. Hyman C, "BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra", Nature, 350, pp.230~232 (1991)
  40. Mö�ssner R, "Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF)", Neurochem Int, 36, pp.197~202 (2000)
  41. Shimizu E, "Ethnic difference of the BDNF 196G", A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits, 2004, pp.126B, 122~123
  42. Wellcome Trust Case Control Consortium., "Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls", Nature, 447, pp.661~578 (2007)
  43. Baum AE, "A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder", Mol Psychiatry, 13, pp.197~207 (2008)

관련 논문AI추천

Association between the BDNF Val66Met Polymorphism and Chronicity of Depression김도관, 김선우, 김수연, 김진우, 명우재, 송지혜, 이유진, 임신원, 정재원, Bernard J Carroll대한신경정신의학회 · PSYCHIATRY INVESTIGATION2013 · 제10권 제1호Lack of Association between Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphisms and Generalized Social Anxiety Disorder in Korean Population오강섭, 이민수, 임세원, Jin-Sung Park, Juwon Ha대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2011 · 제9권 제3호Brain-derived Neurotrophic Factor Val66Met 다형성과 정신분열병의 연합 연구김대진, 김용구, 이화영대한생물정신의학회 · 생물정신의학2006 · 제13권 제4호The rs6265 Polymorphism of the BDNF Gene Is Related to Higher-Lethality Suicide Attempts in the Korean Population원승희, Kang Seung-Gul, Kim Hee-Cheol, Lee Jong Hun, Lee Kwanghun, Seo Wan Seok대한신경정신의학회 · PSYCHIATRY INVESTIGATION2020 · 제17권 제5호Polymorphisms of BDNF Gene and Autism Spectrum Disorders: Family Based Association Study with Korean Trios김순애, 박미라, 양소영, 유희정, 조인희대한신경정신의학회 · PSYCHIATRY INVESTIGATION2014 · 제11권 제3호196G/A of the Brain-Derived Neurotrophic Factor Gene Polymorphisms Predicts Suicidal Behavior in Schizophrenia PatientsEun-Jeong Kim, Yong-Ku Kim대한신경정신의학회 · PSYCHIATRY INVESTIGATION2018 · 제15권 제7호

이 간행물의 다른 논문 (7건)