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Category: rs6265

brain-derived neurotrophic factor gene
Single-nucleotide polymorphism

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Single nucleotide polymorphism (help)
Name(s): Val66Met, V66M, G196A
Gene: BDNF
Chromosome: 11
Region: missing region
Databases: Human SNPView, HapMap,

SNPedia, Wikipedia


AlzGene: Meta-analysis, Overview
SzGene: Meta-analysis, Overview
PDGene: Meta-analysis, Overview

Rs6265, also called Val66Met or G196A, is a gene variation, a single nucleotide polymorphism (SNP) in the BDNF gene that codes for the so-called brain-derived neurotrophic factor.

Well over hundred research studies have examined the polymorphism.

The G-allele is usually the most common.


[edit] Association with neuropsychiatric disorders

A number of studies has examined the polymorphism in relation to neuropsychiatric disorders, such as depression.[1] It is generally thought that some variants of the polymorphism lead to memory impairment and susceptibility to neuropsychiatric disorders,[2] and a 2007 meta-analysis of case-control studies found a relationship between the SNP and substance-related disorders, eating disorders, and schizophrenia.[3] Another 2007 meta-analysis could, however, find no association between the SNP and schizophrenia or bipolar disorder.[4] Meta-analyses of Alzheimer's disease and Parkinson's disease also indicate that the SNP has little or no association with these diseases.[5][6] Also inconsistencies in association studies with depression have been noted.[7]

In treatment response studies val/val homozygotes may respond better than met allele carriers with drug resistant depression treated with repetitive transcranial magnetic stimulation.[8]

[edit] Subject variables in healthy humans

One study has reported that met/met carriers tends to have lower body mass index compared to the two other genotypes.[9] Another study showed that subjects with the val/val genotype had higher mean intelligence.[10]

[edit] Personality genetics

BDNF val66met is associated with introversion and interacts with 5-HTTLPR to influence neuroticism is a meta-analysis on val66met and neuroticism.

[edit] Individual studies

  1. A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression
  2. Association between brain-derived neurotrophic factor 196 G/A polymorphism and personality traits in healthy subjects
  3. Shih-Jen Tsai, Chen-Jee Hong, Younger W.-Y. Yuc, Tai-Jui Chen (2004). "Association study of a brain-derived neurotrophic factor (BDNF) val66met polymorphism and personality trait and intelligence in healthy young females". Biological Psychiatry 49: 13-16. doi: 10.1159/000075333. This study found no association with personality traits as measured with the Tridimensional Personality Questionnaire
  4. Undine E. Lang, Rainer Hellweg, Peter Kalus, Malek Bajbouj, Kirsten P. Lenzen, Thomas Sander, Dieter Kunz, Jürgen Gallinat (2005). "Association of a functional BDNF polymorphism and anxiety-related personality traits". Psychopharmacology (Berlin) 180(1): 95-99. doi: 10.1007/s00213-004-2137-7. PMID: 15918078. This German 2005 study could though find an association with personality traits measured with NEO-Five Factor Inventory, with Val/Val subjects scoring higher on anxiety and neuroticism dimensions.
  5. Association study of candidate variants from brain-derived neurotrophic factor and dystrobrevin-binding protein 1 with neuroticism, anxiety, and depression
  6. A Polish 2007 study observed no significant relationship between the polymorphism and personality in healthy females: Rybakowski F, Dmitrzak-Weglarz M, Szczepankiewicz A, Skibinska M, Slopien A, Rajewski A, Hauser J (2007). "Brain derived neurotrophic factor gene Val66Met and -270C/T polymorphisms and personality traits predisposing to anorexia nervosa". Neuro Endocrinol. Lett. 28(2): 153-158. PMID: 17435670.
  7. Interaction between BDNF val66met and dopamine transporter gene variation influences anxiety-related traits
  8. Interaction between brain-derived neurotrophic factor val66met polymorphism and recent negative stressor in harm avoidance
  9. Interactions between BDNF val66met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety
  10. No evidence for an association between the BDNF val66met polymorphism and schizophrenia or personality traits
  11. The val66met coding variant of the brain-derived neurotrophic factor (BDNF) gene does not contribute toward variation in the personality trait neuroticism

[edit] Other studies

A study in transgenic mice has found that met/met mice exhibits increased anxiety-related behaviors.[11]

[edit] List

  1. Brain derived neurotrophic factor val66met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness

[edit] References

  1. L. Ribeiro L, J. V. Busnello, R. M. Cantor, F. Whelan, P. Whittaker, P. Deloukas, M. L. Wong, J. Licinio (2007). "The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans". NeuroReport 18(12): 1291-1293. PMID: 17632285.
  2. Kevin G. Bath, Francis S. Lee (2006). "Variant BDNF (Val66Met) impact on brain structure and function". Cognitive, Affective, & Behavioral Neuroscience 6(1): 79-85. PMID: 16869232.
  3. Mònica Gratacòs, Juan R. González, Josep M. Mercader, Rafael de Cid, Mikel Urretavizcaya, Xavier Estivill (2007). "Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia". Biological Psychiatry 61(7): 911–912. doi: 10.1016/j.biopsych.2006.08.025. PMID: 17217930.
  4. Kanazawa, Tetsufumi, Glatt, Stephen J., Kia-Keating, Brett, Yoneda, Hiroshi, Tsuang, Ming T (2007). "Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder". Psychiatric Genetics 17(3): 165-170.
  6. E. Zintzaras, G. M. Hadjigeorgiou (2005). "The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis". J. Hum. Genet. 50(11): 560-566. PMID: 16172806.
  7. J. O. Groves (2007). "Is it time to reassess the BDNF hypothesis of depression?". Molecular psychiatry 12(12): 1079–1078. doi: 10.1038/ PMID: 17700574.
  8. Luisella Bocchio-Chiavetto, Carlo Miniussi, Roberta Zanardini, Anna Gazzoli, Stefano Bignotti, Claudia Specchia, Massimo Gennarelli (2008). "5-HTTLPR and BDNF Val66Met polymorphisms and response to rTMS treatment in drug resistant depression". Neuroscience Letters 437(2): 130–134. doi: 10.1016/j.neulet.2008.04.005. PMID: 18450378.
  9. John Gunstad, Peter Schofield, Robert H. Paul, Mary Beth Spitznagel, Ronald A. Cohen, Leanne M. Williams, Michael Kohn, Evian Gordon (2006). "BDNF Val66Met Polymorphism Is Associated with Body Mass Index in Healthy Adults". Neuropsychobiology 53: 153-156. doi: 10.1159/000093341.
  10. Shih-Jen Tsaia, Chen-Jee Hong, Younger W.-Y. Yuc, Tai-Jui Chen (2004). "Association Study of a Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism and Personality Trait and Intelligence in Healthy Young Females". Biological Psychiatry 49: 13-16. doi: 10.1159/000075333.
  11. Zhe-Yu Chen, Deqiang Jing, Kevin G. Bath, Alessandro Ieraci, Tanvir Khan, Chia-Jen Siao, Daniel G. Herrera, Miklos Toth, Chingwen Yang, Bruce S. McEwen, Barbara L. Hempstead (2006). "Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior". Science 314(5796): 140–143.. doi: 10.1126/science.1129663. PMID: 17023662.
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