Academic Journal
An antisense lncRNA mediated mechanism controls desmoplakin gene expression
| العنوان: | An antisense lncRNA mediated mechanism controls desmoplakin gene expression |
|---|---|
| المؤلفون: | De Bortoli, M, Foco, L, Frommelt, L S, Riekschnitz, D A, Volani, C, Motta, B M, Fuchsberger, C, Pramstaller, P P, Pattaro, C, Rossini, A |
| المصدر: | Cardiovascular Research ; volume 120, issue Supplement_1 ; ISSN 0008-6363 1755-3245 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| الوصف: | Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol (Italy). Background Desmosomal genes are established as definitive genes for Arrhythmogenic Cardiomyopathy (ACM). The desmoplakin encoding gene, DSP, is amongst the most frequently mutated genes in ACM patients. While rare genetic variants within desmosomal genes can cause ACM, common variants might also affect cardiac conduction traits in the general population. Purpose 1) To explore the association between common genetic variants in ACM desmosomal genes (DSC2, DSG2, PKP2, JUP, DSP) and cardiac conduction traits. 2) To investigate the effect of a lncRNA, identified from downstream analyses, on DSP gene expression. Methods P-wave, PR, QRS and QT intervals were measured using standard 12-lead electrocardiograms (ECG) in 4295 participants to the Cooperative Health Research in South Tyrol (CHRIS) study (data release 2). Samples were genotyped using the Illumina HumanOmniExpressExome array and imputed on the 1000 Genome Phase 1 panel. We conducted a genetic association study on 3458 variants within the linkage disequilibrium blocks that encompass desmosomal genes, assuming an additive genetic model, at 1.9x10-4 statistical significance. Mendelian Randomization (MR) analyses integrating ECG traits and Genotype-Tissue Expression (GTEx) database transcription levels were performed. A specific GapmeR was used to downregulate the antisense RP3-512B11.3 lncRNA expression in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs lysates were analyzed by digital droplet PCR and Wes™ immunoassay system. Results The rs2744389 variant in DSP gene is associated with a shorter QRS interval (-1.10 ms per effect allele copy; p=3.5x10-6). In the GTEx database, rs2744389 is identified as an expression quantitative trait locus for the antisense lncRNA. MR results support a causal effect of the lncRNA on ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/cvr/cvae088.109 |
| الاتاحة: | http://dx.doi.org/10.1093/cvr/cvae088.109 https://academic.oup.com/cardiovascres/article-pdf/120/Supplement_1/cvae088.109/57953761/cvae088.109.pdf |
| Rights: | https://academic.oup.com/pages/standard-publication-reuse-rights |
| رقم الانضمام: | edsbas.D012802A |
| قاعدة البيانات: | BASE |
كن أول من يترك تعليقا!