rs6265
SNP: rs6265 | |
---|---|
Name(s) | Val66Met, V66M, G196A |
HapMap | 6265 |
SNPedia | 6265 |
AlzGene | Meta-analysis Overview |
SzGene | Meta-analysis Overview |
PDGene | Meta-analysis Overview |
Rs6265, also called Val66Met or G196A, is a gene variation, a
Well over a hundred research studies have examined the polymorphism.
Association with neuropsychiatric disorders
A number of studies have examined the role of this
The reason for these inconsistent results have been suggested to stem from several sources, with one recent review arguing that statistical artefact, sampling bias, population stratification and uncontrolled gene-environment interactions are likely to underscore this effect [1] . These same authors recently published a report which found that transgenic mice engineered to express human BDNF as well as carry the Val66Met permutation are selectively sensitive to the glucocorticoid stress hormone corticosterone (rodent equivalent of cortisol), which in turn primes the fear circuitry and hippocampus-dependent memory function of Met/Met homozygous mice [10] . As hippocampal function is a core component of several psychiatric conditions, and stress is a non-specific but substantial risk factor for affective, anxiety, eating and psychotic disorders, Notaras et al. argue that "there is a long-term effect of glucocorticoids in 66Met carriers that potentiates the fear circuitry into adulthood, which may increase susceptibility to trauma, events with negative emotional valence and related psychopathology".[10] This interpretation is consistent with a suggested role of BDNF and the Val66Met polymorphism in post-traumatic stress disorder,[1][11] where it has been shown that 66Met variant perturbs extinction learning in both man and mouse.[12] The Val66Met polymorphism alters vulnerability to stress in mice and humans, which likely contributes to PTSD risk.[13]
In treatment response studies val/val homozygotes may respond better than met allele carriers with drug resistant depression treated with
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.[15] Another study showed that subjects with the val/val genotype had higher mean intelligence. The same study found no association with
Other studies
A study in transgenic mice has found that met/met mice exhibits increased anxiety-related behaviors.[20]
References
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: CS1 maint: multiple names: authors list (link - S2CID 25579523.
- ^ "META-ANALYSIS OF ALL PUBLISHED AD ASSOCIATION STUDIES (CASE-CONTROL ONLY) rs6265". Alzheimer Research Forum. Archived from the original on 2013-02-23. Retrieved 2008-06-20.
- PMID 16172806.
- PMID 17700574.
- ^ PMID 26821977.
- PMID 23319005.
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- S2CID 209540967.
- S2CID 36187651.)
{{cite journal}}
: CS1 maint: multiple names: authors list (link - S2CID 45218374.
- S2CID 45591436.
- PMID 17435670.
- S2CID 32939759.
- PMID 20042999.
- PMID 17023662.