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Start Over Author "Gentschew L" Journal nature communications
2 results on '"Gentschew L"'

1. Publisher Correction: Identification and characterization of two functional variants in the human longevity gene FOXO3.

Author

Flachsbart F, Dose J, Gentschew L, Geismann C, Caliebe A, Knecht C, Nygaard M, Badarinarayan N, ElSharawy A, May S, Luzius A, Torres GG, Jentzsch M, Forster M, Häsler R, Pallauf K, Lieb W, Derbois C, Galan P, Drichel D, Arlt A, Till A, Krause-Kyora B, Rimbach G, Blanché H, Deleuze JF, Christiansen L, Christensen K, Nothnagel M, Rosenstiel P, Schreiber S, Franke A, Sebens S, and Nebel A

Abstract

The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2018
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2. Identification and characterization of two functional variants in the human longevity gene FOXO3.

Author

Flachsbart F, Dose J, Gentschew L, Geismann C, Caliebe A, Knecht C, Nygaard M, Badarinarayan N, ElSharawy A, May S, Luzius A, Torres GG, Jentzsch M, Forster M, Häsler R, Pallauf K, Lieb W, Derbois C, Galan P, Drichel D, Arlt A, Till A, Krause-Kyora B, Rimbach G, Blanché H, Deleuze JF, Christiansen L, Christensen K, Nothnagel M, Rosenstiel P, Schreiber S, Franke A, Sebens S, and Nebel A

Subjects
Age Factors, Aged, Aged, 80 and over, Alleles, CCCTC-Binding Factor genetics, CCCTC-Binding Factor metabolism, Computer Simulation, Female, Forkhead Box Protein O3 genetics, Haplotypes genetics, Humans, Insulin-Like Growth Factor I metabolism, Introns genetics, Male, Middle Aged, RNA, Messenger metabolism, Serum Response Factor genetics, Serum Response Factor metabolism, Forkhead Box Protein O3 physiology, Longevity genetics, Polymorphism, Single Nucleotide genetics, White People genetics
Abstract

FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.

Published
2017
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