MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy
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MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy. / Girdauskas, Evaldas; Petersen, Johannes; Neumann, Niklas; Ungelenk, Martin; Kurth, Ingo; Reichenspurner, Hermann; Zeller, Tanja.
in: PLOS ONE, Jahrgang 13, Nr. 7, 2018, S. e0200205.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy
AU - Girdauskas, Evaldas
AU - Petersen, Johannes
AU - Neumann, Niklas
AU - Ungelenk, Martin
AU - Kurth, Ingo
AU - Reichenspurner, Hermann
AU - Zeller, Tanja
PY - 2018
Y1 - 2018
N2 - MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the NOTCH1 gene as being the most common finding. Univariate analysis between blood miRNAs and NOTCH1 variants revealed a significantly lower expression of miR-145 in the subgroup of patients with NOTCH1 variants vs. those without NOTCH1 variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare NOTCH1 variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy.
AB - MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the NOTCH1 gene as being the most common finding. Univariate analysis between blood miRNAs and NOTCH1 variants revealed a significantly lower expression of miR-145 in the subgroup of patients with NOTCH1 variants vs. those without NOTCH1 variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare NOTCH1 variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy.
KW - Aortic Valve/abnormalities
KW - Bicuspid Aortic Valve Disease
KW - Biomarkers/blood
KW - Cross-Sectional Studies
KW - Female
KW - Follow-Up Studies
KW - Gene Expression
KW - Genetic Association Studies
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Heart Valve Diseases/blood
KW - Humans
KW - Male
KW - MicroRNAs/blood
KW - Middle Aged
KW - Preliminary Data
KW - Receptor, Notch1/genetics
U2 - 10.1371/journal.pone.0200205
DO - 10.1371/journal.pone.0200205
M3 - SCORING: Journal article
C2 - 30059548
VL - 13
SP - e0200205
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
ER -
