Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome.
<h4>Background</h4>Brugada syndrome (BrS) can be diagnosed by a type 1 BrS tracing in a 12-lead electrocardiogram (ECG). However, there are daily variations in the ECGs of BrS patients, which presents a challenge when diagnosing BrS. Although many susceptibility genes have been identifie...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0261390 |
| _version_ | 1818048118946529280 |
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| author | Yoshihiro Ikeuchi Hidenori Ochi Chikaaki Motoda Takehito Tokuyama Yousaku Okubo Sho Okamura Syunsuke Miyauchi Shogo Miyamoto Yukimi Uotani Yuko Onohara Mika Nakashima Rie Akiyama Hidetoshi Tahara Kazuaki Chayama Yasuki Kihara Yukiko Nakano |
| author_facet | Yoshihiro Ikeuchi Hidenori Ochi Chikaaki Motoda Takehito Tokuyama Yousaku Okubo Sho Okamura Syunsuke Miyauchi Shogo Miyamoto Yukimi Uotani Yuko Onohara Mika Nakashima Rie Akiyama Hidetoshi Tahara Kazuaki Chayama Yasuki Kihara Yukiko Nakano |
| author_sort | Yoshihiro Ikeuchi |
| collection | DOAJ |
| description | <h4>Background</h4>Brugada syndrome (BrS) can be diagnosed by a type 1 BrS tracing in a 12-lead electrocardiogram (ECG). However, there are daily variations in the ECGs of BrS patients, which presents a challenge when diagnosing BrS. Although many susceptibility genes have been identified, the SCN5A gene is reportedly the main causative gene of BrS. However, most patients do not have an evidence of genetic predisposition to develop BrS. In addition, the diagnosis and risk stratification for ventricular fibrillation (VF) in patients with BrS presents some problems. Meanwhile, circulating micro RNAs (miRNAs) have drawn increased attention as potential biomarkers of various diseases. We hypothesize that circulating miRNAs may be potential diagnostic biomarkers for BrS.<h4>Methods</h4>We enrolled 70 Japanese BrS patients and 34 controls for the screening cohort. A total of 2,555 miRNA sequences were detected using the 3D-Gene miRNAs labeling kit and 3D-Gene Human miRNAs Oligo Chip. We compared the expression of the miRNAs between the BrS patients and the controls. We validated whether the miRNA were significantly up- or downregulated in the screening cohort using RT-PCR. We also enrolled 72 Japanese BrS patients and 56 controls to replicate these miRNAs.<h4>Results</h4>Eight miRNAs (hsa-miR-223-3p, hsa-miR-22-3p, hsa-miR-221-3p, hsa-miR-4485-5p, hsa-miR-550a-5p, hsa-miR-423-3p, hsa-miR-23a-3p, and hsa-miR-30d-5p) were downregulated, and one miRNA (hsa-miR-873-3p) was upregulated by more than 3-fold in BrS patients. The multivariate logistic regression analysis determined that hsa-miR-423-3p, hsa-miR-223-3p, and hsa-miR-23a-3p were independently associated with BrS (P < 0.0001). The AUC based on cross validation was 0.871 with a sensitivity and specificity of 83.5% and 81.1%, respectively.<h4>Conclusions</h4>The plasma miRNAs are potential noninvasive biomarkers of BrS, and the constructed logistic model was useful for discriminating BrS. |
| first_indexed | 2024-12-10T10:16:37Z |
| format | Article |
| id | doaj.art-fcdf6ed586274556b8081847bae72ca2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T10:16:37Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fcdf6ed586274556b8081847bae72ca22022-12-22T01:52:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175e026139010.1371/journal.pone.0261390Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome.Yoshihiro IkeuchiHidenori OchiChikaaki MotodaTakehito TokuyamaYousaku OkuboSho OkamuraSyunsuke MiyauchiShogo MiyamotoYukimi UotaniYuko OnoharaMika NakashimaRie AkiyamaHidetoshi TaharaKazuaki ChayamaYasuki KiharaYukiko Nakano<h4>Background</h4>Brugada syndrome (BrS) can be diagnosed by a type 1 BrS tracing in a 12-lead electrocardiogram (ECG). However, there are daily variations in the ECGs of BrS patients, which presents a challenge when diagnosing BrS. Although many susceptibility genes have been identified, the SCN5A gene is reportedly the main causative gene of BrS. However, most patients do not have an evidence of genetic predisposition to develop BrS. In addition, the diagnosis and risk stratification for ventricular fibrillation (VF) in patients with BrS presents some problems. Meanwhile, circulating micro RNAs (miRNAs) have drawn increased attention as potential biomarkers of various diseases. We hypothesize that circulating miRNAs may be potential diagnostic biomarkers for BrS.<h4>Methods</h4>We enrolled 70 Japanese BrS patients and 34 controls for the screening cohort. A total of 2,555 miRNA sequences were detected using the 3D-Gene miRNAs labeling kit and 3D-Gene Human miRNAs Oligo Chip. We compared the expression of the miRNAs between the BrS patients and the controls. We validated whether the miRNA were significantly up- or downregulated in the screening cohort using RT-PCR. We also enrolled 72 Japanese BrS patients and 56 controls to replicate these miRNAs.<h4>Results</h4>Eight miRNAs (hsa-miR-223-3p, hsa-miR-22-3p, hsa-miR-221-3p, hsa-miR-4485-5p, hsa-miR-550a-5p, hsa-miR-423-3p, hsa-miR-23a-3p, and hsa-miR-30d-5p) were downregulated, and one miRNA (hsa-miR-873-3p) was upregulated by more than 3-fold in BrS patients. The multivariate logistic regression analysis determined that hsa-miR-423-3p, hsa-miR-223-3p, and hsa-miR-23a-3p were independently associated with BrS (P < 0.0001). The AUC based on cross validation was 0.871 with a sensitivity and specificity of 83.5% and 81.1%, respectively.<h4>Conclusions</h4>The plasma miRNAs are potential noninvasive biomarkers of BrS, and the constructed logistic model was useful for discriminating BrS.https://doi.org/10.1371/journal.pone.0261390 |
| spellingShingle | Yoshihiro Ikeuchi Hidenori Ochi Chikaaki Motoda Takehito Tokuyama Yousaku Okubo Sho Okamura Syunsuke Miyauchi Shogo Miyamoto Yukimi Uotani Yuko Onohara Mika Nakashima Rie Akiyama Hidetoshi Tahara Kazuaki Chayama Yasuki Kihara Yukiko Nakano Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. PLoS ONE |
| title | Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. |
| title_full | Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. |
| title_fullStr | Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. |
| title_full_unstemmed | Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. |
| title_short | Plasma MicroRNAs as noninvasive diagnostic biomarkers in patients with Brugada syndrome. |
| title_sort | plasma micrornas as noninvasive diagnostic biomarkers in patients with brugada syndrome |
| url | https://doi.org/10.1371/journal.pone.0261390 |
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