Genetic variation in FGF20 modulates hippocampal biology.

H. Lemaitre, V. S. Mattay, F. Sambataro, B. Verchinski, R. E. Straub, J. H. Callicott, R. Kittappa, T. M. Hyde, B. K. Lipska, J. E. Kleinman, R. McKay, D. R. Weinberger
Journal of Neuroscience. 2010-04-28; 30(17): 5992-5997
DOI: 10.1523/JNEUROSCI.5773-09.2010

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We explored the effect of single-nucleotide polymorphisms (SNPs) in the
fibroblast growth factor 20 gene (FGF20) associated with risk for Parkinson’s
disease on brain structure and function in a large sample of healthy young-adult
human subjects and also in elderly subjects to look at the interaction between
genetic variations and age (N = 237; 116 men; 18-87 years). We analyzed
high-resolution anatomical magnetic resonance images using voxel-based
morphometry, a quantitative neuroanatomical technique. We also measured FGF20
mRNA expression in postmortem human brain tissue to determine the molecular
correlates of these SNPs (N = 108; 72 men; 18-74 years). We found that the T
allele carriers of rs12720208 in the 3′-untranslated region had relatively larger
hippocampal volume (p = 0.0059) and diminished verbal episodic memory (p = 0.048)
and showed steeper decreases of hippocampal volume with normal aging (p = 0.026).
In postmortem brain, T allele carriers had greater expression of hippocampal
FGF20 mRNA (p = 0.037), consistent with a previously characterized microRNA
mechanism. The C allele matches a predicted miR-433 microRNA binding domain,
whereas the T allele disrupts it, resulting in higher FGF20 protein translation.
The strong FGF20 genetic effects in hippocampus are presumably mediated by
activation of the FGFR1 (FGF receptor 1), which is expressed in mammalian brain
most abundantly in the hippocampus. These associations, from mRNA expression to
brain morphology to cognition and an interaction with aging, confirm a role of
FGF20 in human brain structure and function during development and aging.

Auteurs Bordeaux Neurocampus