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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.

Association with neuropsychiatric disorders Edit

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]

Subject variables in healthy humans Edit

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. The same study found no association with personality traits as measured with the Tridimensional Personality Questionnaire.[10] Also a Polish 2007 study observed no significant relationship between the polymorphism and personality in healthy females.[11] A 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.[12]

Other studies Edit

A study in transgenic mice has found that met/met mice exhibits increased anxiety-related behaviors.[13]

References Edit

  1. Ribeiro L, Busnello JV, Cantor RM, Whelan F, Whittaker P, Deloukas P, Wong ML, Licinio J (August 2007). The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. NeuroReport 18 (12): 1291-1293.
  2. Kevin G. Bath & Francis S. Lee (March 2006). Variant BDNF (Val66Met) impact on brain structure and function. Cognitive, Affective, & Behavioral Neuroscience 6 (1): 79-85.
  3. Mònica Gratacòs, Juan R. González, Josep M. Mercader, Rafael de Cid, Mikel Urretavizcaya & Xavier Estivill (April 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.
  4. Kanazawa, Tetsufumi; Glatt, Stephen J.; Kia-Keating, Brett; Yoneda, Hiroshi; Tsuang, Ming T (June 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.
  5. META-ANALYSIS OF ALL PUBLISHED AD ASSOCIATION STUDIES (CASE-CONTROL ONLY) rs6265. Alzheimer Research Forum. URL accessed on 2008-06-20.
  6. E. Zintzaras E, 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.
  7. J. O. Groves (December 2007). Is it time to reassess the BDNF hypothesis of depression?. Molecular psychiatry 12 (12): 1079–1078.
  8. Luisella Bocchio-Chiavetto, Carlo Miniussi, Roberta Zanardini, Anna Gazzoli, Stefano Bignotti, Claudia Specchia & Massimo Gennarelli (May 2008). 5-HTTLPR and BDNF Val66Met polymorphisms and response to rTMS treatment in drug resistant depression. Neuroscience Letters 437 (2): 130–134.
  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.
  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.
  11. Rybakowski F, Dmitrzak-Weglarz M, Szczepankiewicz A, Skibinska M, Slopien A, Rajewski A, Hauser J (April 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.
  12. Undine E. Lang, Rainer Hellweg, Peter Kalus, Malek Bajbouj, Kirsten P. Lenzen4, Thomas Sander, Dieter Kunz and Jürgen Gallinat (June 2005). Association of a functional BDNF polymorphism and anxiety-related personality traits. Psychopharmacology (Berlin) 180 (1): 95-99.
  13. 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, and Francis S. Lee (October 2006). Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior. Science 314 (5796): 140–143..
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