Rs6265

Infobox Single nucleotide polymorphism
rsid = 6265
name_1 = Val66Met
name_2 = V66M
name_3 = G196A
gene = BDNF
chromosome = 11
alzgene_geneid = 109
alzgene_polyid = 334
pdgene_geneid = 4
pdgene_polyid = 13
szgene_geneid = 2
szgene_polyid = 28

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

A number of studies has examined the polymorphism in relation to neuropsychiatric disorders, such as depression. [Cite journal
author = Ribeiro L, Busnello JV, Cantor RM, Whelan F, Whittaker P, Deloukas P, Wong ML, Licinio J
title = The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans
journal = NeuroReport
year = 2007
month = August
volume = 6
volume = 18
issue = 12
pages = 1291-1293
pmid = 17632285] It is generally thought that some variants of the polymorphism lead to memory impairment and susceptibility to neuropsychiatric disorders, [Cite journal
author = Kevin G. Bath & Francis S. Lee
title = Variant BDNF (Val66Met) impact on brain structure and function
journal = Cognitive, Affective, & Behavioral Neuroscience
year = 2006
month = March
volume = 6
issue = 1
pages = 79-85
pmid = 16869232] and a 2007 meta-analysis of case-control studies found a relationship between the SNP and substance-related disorders, eating disorders, and schizophrenia. [Cite journal
author = Mònica Gratacòs, Juan R. González, Josep M. Mercader, Rafael de Cid, Mikel Urretavizcaya & Xavier Estivill
title = Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia
journal = Biological Psychiatry
volume = 61
issue = 7
pages = 911–912
year = 2007
month = April
doi = 10.1016/j.biopsych.2006.08.025
pmid = 17217930] Another 2007 meta-analysis could, however, find no association between the SNP and schizophrenia or bipolar disorder. [Cite journal
author = Kanazawa, Tetsufumi; Glatt, Stephen J.; Kia-Keating, Brett; Yoneda, Hiroshi; Tsuang, Ming T
title = Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder
journal = Psychiatric Genetics
volume = 17
issue = 3
pages = 165-170
month = June
year = 2007
url = http://www.psychgenetics.com/pt/re/psychgen/abstract.00041444-200706000-00006.htm;jsessionid=LbhYbtH3v8Lryl56CC97wFG5rcLHNyn71X03GL8R5p2YT227L4LS!2016747336!181195628!8091!-1] Meta-analyses of Alzheimer's disease and Parkinson's disease also indicate that the SNP has little or no association with these diseases. [Cite web
title = META-ANALYSIS OF ALL PUBLISHED AD ASSOCIATION STUDIES (CASE-CONTROL ONLY) rs6265
url = http://www.alzforum.org/res/com/gen/alzgene/meta.asp?geneID=109&polyID=334
publisher = Alzheimer Research Forum
accessdate = 2008-06-20] [Cite journal
author = E. Zintzaras E, G. M. Hadjigeorgiou
title = The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson's disease: a meta-analysis
journal = J. Hum. Genet.
year = 2005
volume = 50
issue =11
pages = 560-566
pmid = 16172806] Also inconsistencies in association studies with depression have been noted. [Cite journal
author = J. O. Groves
title = Is it time to reassess the BDNF hypothesis of depression?
journal = Molecular psychiatry
volume = 12
issue = 12
pages = 1079–1078
year = 2007
month = December
doi = 10.1038/sj.mp.4002075
pmid = 17700574]

In treatment response studies val/val homozygotes may respond better than met allele carriers with drug resistant depression treated with repetitive transcranial magnetic stimulation. [Cite journal
author = Luisella Bocchio-Chiavetto, Carlo Miniussi, Roberta Zanardini, Anna Gazzoli, Stefano Bignotti, Claudia Specchia & Massimo Gennarelli
title = 5-HTTLPR and BDNF Val66Met polymorphisms and response to rTMS treatment in drug resistant depression
journal = Neuroscience Letters
volume = 437
issue = 2
pages = 130–134
year = 2008
month = May
doi = 10.1016/j.neulet.2008.04.005
pmid = 18450378]

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. [Cite journal
author = John Gunstad, Peter Schofield, Robert H. Paul, Mary Beth Spitznagel, Ronald A. Cohen, Leanne M. Williams, Michael Kohn, Evian Gordon
title = BDNF Val66Met Polymorphism Is Associated with Body Mass Index in Healthy Adults
journal = Neuropsychobiology
year = 2006
volume = 53
pages = 153-156
doi = 10.1159/000093341
url = http://content.karger.com/ProdukteDB/produkte.asp?Doi=93341] 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. [Cite journal
author = Shih-Jen Tsaia, Chen-Jee Hong, Younger W.-Y. Yuc, Tai-Jui Chen
title = Association Study of a Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism and Personality Trait and Intelligence in Healthy Young Females
journal = Biological Psychiatry
year = 2004
volume = 49
pages = 13-16
doi = 10.1159/000075333] Also a Polish 2007 study observed no significant relationship between the polymorphism and personality in healthy females. [Cite journal
author = Rybakowski F, Dmitrzak-Weglarz M, Szczepankiewicz A, Skibinska M, Slopien A, Rajewski A, Hauser J
title = Brain derived neurotrophic factor gene Val66Met and -270C/T polymorphisms and personality traits predisposing to anorexia nervosa
journal = Neuro Endocrinol. Lett.
year = 2007
month = April
volume = 28
issue = 2
pages = 153-158
pmid = 17435670 ] 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. [Cite journal
author = Undine E. Lang, Rainer Hellweg, Peter Kalus, Malek Bajbouj, Kirsten P. Lenzen4, Thomas Sander, Dieter Kunz and Jürgen Gallinat
title = Association of a functional BDNF polymorphism and anxiety-related personality traits
journal = Psychopharmacology (Berlin)
year = 2005
month = June
volume = 180
issue = 1
pages = 95-99
pmid = 15918078
doi = 10.1007/s00213-004-2137-7]

Other studies

A study in transgenic mice has found that met/met mice exhibits increased anxiety-related behaviors. [Cite journal
author = 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
title = Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior
journal = Science
year = 2006
month = October
volume = 314
issue = 5796
pages = 140–143.
doi = 10.1126/science.1129663
pmc = 1880880
pmid = 17023662]

References