scholarly journals Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2019 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Large Fraction ◽  
Axonal Growth ◽  
Long Term Potentiation ◽  
Genetic Risk Factor ◽  
Dependent Manner ◽  
Genome Wide ◽  
Term Potentiation ◽  
App Metabolism

ABSTRACTAlthough APP metabolism is being intensively investigated, a large fraction of its modulators are yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a genetic risk factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance; a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism and that FERMT2 under-expression impacts axonal growth, synaptic connectivity and long-term potentiation in an APP-dependent manner. Lastly, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3’UTR of FERMT2, induced a down-regulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 under-expression in neurons and insight on how this may influence AD pathogenesis.

scholarly journals Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2020 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Large Fraction ◽  
Axonal Growth ◽  
Long Term Potentiation ◽  
Genetic Risk Factor ◽  
Dependent Manner ◽  
Genome Wide ◽  
Term Potentiation ◽  
App Metabolism

AbstractAlthough APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a genetic risk factor of Alzheimer’s disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3′UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.

scholarly journals Alzheimer's genetic risk factor FERMT2 (kindlin‐2) controls axonal growth and synaptic plasticity in an APP‐dependent manner

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Fanny Eysert ◽  
AudreyAnais‐Camille CoulonVreulx ◽  
Amandine Flaig ◽  
Tiago Mendes ◽  
Benjamin Grenier‐Boley ◽  
...  
Keyword(s):  
Risk Factor ◽  
Synaptic Plasticity ◽  
Genetic Risk ◽  
Axonal Growth ◽  
Genetic Risk Factor ◽  
Dependent Manner

scholarly journals Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism

2016 ◽  
Vol 133 (6) ◽  
pp. 955-966 ◽  
Author(s):  
Julien Chapuis ◽  
◽  
Amandine Flaig ◽  
Benjamin Grenier-Boley ◽  
Fanny Eysert ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Genetic Risk Factor ◽  
Genome Wide ◽  
App Metabolism ◽  
Sirna Screening

scholarly journals Correction to: Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner

2021 ◽  
Author(s):  
Fanny Eysert ◽  
Audrey Coulon ◽  
Emmanuelle Boscher ◽  
Anaїs-Camille Vreulx ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Risk Factor ◽  
Synaptic Plasticity ◽  
Genetic Risk ◽  
Axonal Growth ◽  
Genetic Risk Factor ◽  
Dependent Manner

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genome-Wide Study Of Interaction Between Season Of Birth and Peanut Allergy Identifies a Region On Chromosome 3 As a Genetic Risk Factor

2014 ◽  
Vol 133 (2) ◽  
pp. AB199
Author(s):  
Corinne Keet ◽  
Xiumei Hong ◽  
Ingo Ruczinski ◽  
Terri H. Beaty ◽  
Jacqueline Pongracic ◽  
...  
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Peanut Allergy ◽  
Genetic Risk Factor ◽  
Chromosome 3 ◽  
Season Of Birth ◽  
Genome Wide ◽  
Genome Wide Study

scholarly journals Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association Study follow-up

2012 ◽  
Vol 21 (12) ◽  
pp. 2825-2835 ◽  
Author(s):  
Jose-Ezequiel Martin ◽  
Jasper C. Broen ◽  
F. David Carmona ◽  
Maria Teruel ◽  
Carmen P. Simeon ◽  
...  
Keyword(s):  
Risk Factor ◽  
Systemic Sclerosis ◽  
Association Study ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Genetic Risk Factor ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses

PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e20457 ◽  
Author(s):  
Chikashi Terao ◽  
Koichiro Ohmura ◽  
Masaki Katayama ◽  
Meiko Takahashi ◽  
Miki Kokubo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Myelin Basic Protein ◽  
Genetic Risk ◽  
Basic Protein ◽  
Genetic Risk Factor ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Study

scholarly journals Genome-Wide Association Study Identifies a Novel Genetic Risk Factor for Recurrent Venous Thrombosis

2018 ◽  
Vol 11 (2) ◽  
Author(s):  
Hugoline G. de Haan ◽  
Astrid van Hylckama Vlieg ◽  
Marine Germain ◽  
Trevor P. Baglin ◽  
Jean-François Deleuze ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Association Study ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Genetic Risk Factor ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Recurrent Venous Thrombosis

Association after linkage analysis indicates that homozygosity for the 46C→T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis

2004 ◽  
Vol 91 (05) ◽  
pp. 899-904 ◽  
Author(s):  
Isabel Tirado ◽  
José Mateo ◽  
Artur Oliver ◽  
Juan Souto ◽  
Amparo Santamaria ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Genetic Risk ◽  
Case Control ◽  
Genetic Risk Factor ◽  
Factor Xii ◽  
Thrombotic Disease ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

SummaryIn a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism (46C→T) in the F12 locus jointly influences variability of plasma (Factor XII) FXII levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the 46C→T polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls. We measured FXII levels and genotyped the 46C→T polymorphism, as well as a number of classical risk factors for thrombotic disease. We confirmed that individuals with different genotypes for this polymorphism showed significant differences in their FXII levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of thrombosis (adjusted OR of 4.82; 95% CI 1.5-15.6), suggesting that the polymorphism itself is an independent risk factor for venous thromboembolism. This study confirms that the 46C→T polymorphism is a genetic risk factor for venous thrombosis in the Spanish population. In addition, our results confirm that a genome-wide scan coupled with a classical case-control association study is an extremely valuable approach to identify DNA variants that affect complex diseases.

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