Please use this identifier to cite or link to this item:
https://doi.org/10.1038/ncomms15466
| Title: | Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1 | Authors: | Pasutto, F Zenkel, M Hoja, U Berner, D Uebe, S Ferrazzi, F Schödel, J Liravi, P Ozaki, M Paoli, D Frezzotti, P Mizoguchi, T Nakano, S Kubota, T Manabe, S Salvi, E Manunta, P Cusi, D Gieger, C Wichmann, H.-E Aung, T Khor, C.C Kruse, F.E Reis, A Schlötzer-Schrehardt, U |
Keywords: | complementary DNA DNA genomic DNA hepatocyte nuclear factor 4 hepatocyte nuclear factor 4alpha heterodimer immunoglobulin enhancer binding protein immunoglobulin G lysyl oxidase like 1 messenger RNA myogenin nf 1 protein NR2F1 protein oligonucleotide peroxisome proliferator activated receptor alpha peroxisome proliferator activated receptor gamma protein puromycin retinoic acid retinoid X receptor alpha RNA polymerase II roaz protein small interfering RNA transcription factor unclassified drug zid protein LOXL1 protein, human oxidoreductase protein binding retinoid X receptor alpha allele cardiovascular disease chemical binding data assimilation enzyme activity genetic variation protein risk factor allelic imbalance alternative RNA splicing Article binding affinity binding site biotinylation chromosome 15 cohort analysis comparative study controlled study DNA binding DNA probe DNA protein complex enhancer region gel mobility shift assay gene activation gene control gene expression gene locus genetic transfection genetic variability genetic variation genome-wide association study genotype genotype phenotype correlation glaucoma haplotype human human tissue in vitro study intron luciferase assay major clinical study molecular size nonsense mediated mRNA decay polymorphic locus promoter region protein binding protein expression pseudoexfoliation quantitative analysis reverse transcription polymerase chain reaction RNA analysis single nucleotide polymorphism steady state transient transfection upregulation aged allele case control study chemistry chromatin complication female genetic predisposition genetics Germany Italy Japan male middle aged pseudoexfoliation very elderly Aged Aged, 80 and over Alleles Alternative Splicing Amino Acid Oxidoreductases Case-Control Studies Chromatin Enhancer Elements, Genetic Exfoliation Syndrome Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype Germany Glaucoma Humans Introns Italy Japan Male Middle Aged Polymorphism, Single Nucleotide Protein Binding Retinoid X Receptor alpha |
Issue Date: | 2017 | Publisher: | Nature Publishing Group | Citation: | Pasutto, F, Zenkel, M, Hoja, U, Berner, D, Uebe, S, Ferrazzi, F, Schödel, J, Liravi, P, Ozaki, M, Paoli, D, Frezzotti, P, Mizoguchi, T, Nakano, S, Kubota, T, Manabe, S, Salvi, E, Manunta, P, Cusi, D, Gieger, C, Wichmann, H.-E, Aung, T, Khor, C.C, Kruse, F.E, Reis, A, Schlötzer-Schrehardt, U (2017). Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1. Nature Communications 8 : 15466. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms15466 | Rights: | Attribution 4.0 International | Abstract: | Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXR? (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression. © The Author(s) 2017. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/179715 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms15466 | Rights: | Attribution 4.0 International |
| Appears in Collections: | Elements Staff Publications |
Show full item record
Files in This Item:
| File | Description | Size | Format | Access Settings | Version | |
|---|---|---|---|---|---|---|
| 10_1038_ncomms15466.pdf | 1.39 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License
