Circulating microRNA-1a is a biomarker of Graves’ disease patients with atrial fibrillation
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It has been increasingly suggested that specific microRNAs expression profiles in the circulation and atrial tissue are associated with the susceptibility to atrial fibrillation. Nonetheless, the role of circulating microRNAs in Graves’ disease patients with atrial fibrillation has not yet been well described. The objective of the study was to identify the role of circulating microRNAs as specific biomarkers for the diagnosis of Graves’ disease with atrial fibrillation.
The expression profiles of eight serum microRNAs, which are found to be critical in the pathogenesis of atrial fibrillation, were determined in patients with Graves’ disease with or without atrial fibrillation. MicroRNA expression analysis was performed by real-time PCR in normal control subjects (NC; n = 17), patients with Graves’ disease without atrial fibrillation (GD; n = 29), patients with Graves’ disease with atrial fibrillation (GD + AF; n = 14), and euthyroid patients with atrial fibrillation (AF; n = 22).
Three of the eight serum microRNAs,i.e., miR-1a, miR-26a, and miR-133, had significantly different expression profiles among the four groups. Spearman’s correlation analysis showed that the relative expression level of miR-1a was positively correlated with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively related to thyroid stimulating hormone. Spearman’s correlations analysis also revealed that the level of miR-1a was negatively correlated with a critical echocardiographic parameter (left atrial diameter), which was dramatically increased in GD + AF group compared to GD group. Furthermore, the receiver-operating characteristic curve analysis indicated that, among the eight microRNAs, miR-1a had the largest area under the receiver-operating characteristic curves not only for discriminating between individuals with and without Graves’ disease, but also for predicting the presence of atrial fibrillation in patients with Graves’ disease.
Our findings showed that the levels of serum miR-1a were significantly decreased in GD + AF group compared with GD group, suggesting that serum miR-1a might serve as a novel biomarker for diagnosis of atrial fibrillation in patients with Graves’ disease.
KeywordsGraves’ disease Thyroid hormone Atrial fibrillation MicroRNA
This study was supported by the National Natural Science Foundation of China (81400834), Young Talents Training Project of Tongji University (2013KJ092), and a grant of People’s Hospital of Shanghai Putuo District (RYK15-08).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of ethic committees of our hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.M. den Hoed, M. Eijgelsheim, T. Esko, B.J. Brundel, D.S. Peal, D.M. Evans, I.M. Nolte, A.V. Segre, H. Holm, R.E. Handsaker, H.J. Westra, T. Johnson, A. Isaacs, J. Yang, A. Lundby, J.H. Zhao, Y.J. Kim, M.J. Go, P. Almgren, M. Bochud, G. Boucher, M.C. Cornelis, D. Gudbjartsson, D. Hadley, P. van der Harst, C. Hayward, M. den Heijer, W. Igl, A.U. Jackson, Z. Kutalik, J. Luan, J.P. Kemp, K. Kristiansson, C. Ladenvall, M. Lorentzon, M.E. Montasser, O.T. Njajou, P.F. O’Reilly, S. Padmanabhan, B. St Pourcain, T. Rankinen, P. Salo, T. Tanaka, N.J. Timpson, V. Vitart, L. Waite, W. Wheeler, W. Zhang, H.H. Draisma, M.F. Feitosa, K.F. Kerr, P.A. Lind, E. Mihailov, N.C. Onland-Moret, C. Song, M.N. Weedon, W. Xie, L. Yengo, D. Absher, C.M. Albert, A. Alonso, D.E. Arking, P.I. de Bakker, B. Balkau, C. Barlassina, P. Benaglio, J.C. Bis, N. Bouatia-Naji, S. Brage, S.J. Chanock, P.S. Chines, M. Chung, D. Darbar, C. Dina, M. Dorr, P. Elliott, S.B. Felix, K. Fischer, C. Fuchsberger, E.J. de Geus, P. Goyette, V. Gudnason, T.B. Harris, A.L. Hartikainen, A.S. Havulinna, S.R. Heckbert, A.A. Hicks, A. Hofman, S. Holewijn, F. Hoogstra-Berends, J.J. Hottenga, M.K. Jensen, A. Johansson, J. Junttila, S. Kaab, B. Kanon, S. Ketkar, K.T. Khaw, J.W. Knowles, A.S. Kooner, J.A. Kors, M. Kumari, L. Milani, P. Laiho, E.G. Lakatta, C. Langenberg, M. Leusink, Y. Liu, R.N. Luben, K.L. Lunetta, S.N. Lynch, M.R. Markus, P. Marques-Vidal, I. Mateo Leach, W.L. McArdle, S.A. McCarroll, S.E. Medland, K.A. Miller, G.W. Montgomery, A.C. Morrison, M. Muller-Nurasyid, P. Navarro, M. Nelis, J.R. O’Connell, C.J. O’Donnell, K.K. Ong, A.B. Newman, A. Peters, O. Polasek, A. Pouta, P.P. Pramstaller, B.M. Psaty, D.C. Rao, S.M. Ring, E.J. Rossin, D. Rudan, S. Sanna, R.A. Scott, J.S. Sehmi, S. Sharp, J.T. Shin, A.B. Singleton, A.V. Smith, N. Soranzo, T.D. Spector, C. Stewart, H.M. Stringham, K.V. Tarasov, A.G. Uitterlinden, L. Vandenput, S.J. Hwang, J.B. Whitfield, C. Wijmenga, S.H. Wild, G. Willemsen, J.F. Wilson, J.C. Witteman, A. Wong, Q. Wong, Y. Jamshidi, P. Zitting, J.M. Boer, D.I. Boomsma, I.B. Borecki, C.M. van Duijn, U. Ekelund, N.G. Forouhi, P. Froguel, A. Hingorani, E. Ingelsson, M. Kivimaki, R.A. Kronmal, D. Kuh, L. Lind, N.G. Martin, B.A. Oostra, N.L. Pedersen, T. Quertermous, J.I. Rotter, Y.T. van der Schouw, W.M. Verschuren, M. Walker, D. Albanes, D.O. Arnar, T.L. Assimes, S. Bandinelli, M. Boehnke, R.A. de Boer, C. Bouchard, W.L. Caulfield, J.C. Chambers, G. Curhan, D. Cusi, J. Eriksson, L. Ferrucci, W.H. van Gilst, N. Glorioso, J. de Graaf, L. Groop, U. Gyllensten, W.C. Hsueh, F.B. Hu, H.V. Huikuri, D.J. Hunter, C. Iribarren, B. Isomaa, M.R. Jarvelin, A. Jula, M. Kahonen, L.A. Kiemeney, M.M. van der Klauw, J.S. Kooner, P. Kraft, L. Iacoviello, T. Lehtimaki, M.L. Lokki, B.D. Mitchell, G. Navis, M.S. Nieminen, C. Ohlsson, N.R. Poulter, L. Qi, O.T. Raitakari, E.B. Rimm, J.D. Rioux, F. Rizzi, I. Rudan, V. Salomaa, P.S. Sever, D.C. Shields, A.R. Shuldiner, J. Sinisalo, A.V. Stanton, R.P. Stolk, D.P. Strachan, J.C. Tardif, U. Thorsteinsdottir, J. Tuomilehto, D.J. van Veldhuisen, J. Virtamo, J. Viikari, P. Vollenweider, G. Waeber, E. Widen, Y.S. Cho, J.V. Olsen, P.M. Visscher, C. Willer, L. Franke, B.C. Global, C.A. Consortium, J. Erdmann, J.R. Thompson, P.G. Consortium, A. Pfeufer, Q.G. Consortium, N. Sotoodehnia, Q.-I. Consortium, C. Newton-Cheh, C.-A. Consortium, P.T. Ellinor, B.H. Stricker, A. Metspalu, M. Perola, J.S. Beckmann, G.D. Smith, K. Stefansson, N.J. Wareham, P.B. Munroe, O.C. Sibon, D.J. Milan, H. Snieder, N.J. Samani, R.J. Loos, Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nat. Genet. 45(6), 621–631 (2013)CrossRefGoogle Scholar
- 9.M. Hulsmans, P. Sinnaeve, B. Van der Schueren, C. Mathieu, S. Janssens, P. Holvoet, Decreased miR-181a expression in monocytes of obese patients is associated with the occurrence of metabolic syndrome and coronary artery disease. J. Clin. Endocrinol. Metab. 97(7), E1213–E1218 (2012)CrossRefGoogle Scholar
- 10.D.P. Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281–297 (2004)Google Scholar
- 12.M. Karakas, C. Schulte, S. Appelbaum, F. Ojeda, K.J. Lackner, T. Munzel, R.B. Schnabel, S. Blankenberg, T. Zeller Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study. Eur. Heart. J. 38(7), 516–523 (2017)Google Scholar
- 14.P.S. Mitchell, R.K. Parkin, E.M. Kroh, B.R. Fritz, S.K. Wyman, E.L. Pogosova-Agadjanyan, A. Peterson, J. Noteboom, K.C. O’Briant, A. Allen, D.W. Lin, N. Urban, C.W. Drescher, B.S. Knudsen, D.L. Stirewalt, R. Gentleman, R.L. Vessella, P.S. Nelson, D.B. Martin, M. Tewari, Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. U. S. A. 105(30), 10513–10518 (2008)PubMedCentralCrossRefGoogle Scholar
- 18.X. Luo, Z. Pan, H. Shan, J. Xiao, X. Sun, N. Wang, H. Lin, L. Xiao, A. Maguy, X.Y. Qi, Y. Li, X. Gao, D. Dong, Y. Zhang, Y. Bai, J. Ai, L. Sun, H. Lu, X.Y. Luo, Z. Wang, Y. Lu, B. Yang, S. Nattel, MicroRNA-26 governs profibrillatory inward-rectifier potassium current changes in atrial fibrillation. J. Clin. Invest. 123(5), 1939–1951 (2013)PubMedCentralCrossRefGoogle Scholar
- 20.R.F. Duisters, A.J. Tijsen, B. Schroen, J.J. Leenders, V. Lentink, I. van der Made, V. Herias, R.E. van Leeuwen, M.W. Schellings, P. Barenbrug, J.G. Maessen, S. Heymans, Y.M. Pinto, E.E. Creemers, miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ. Res. 104(2), 170–178 (2009). 176p following 178CrossRefGoogle Scholar
- 23.T.Y. Ling, X.L. Wang, Q. Chai, T.W. Lau, C.M. Koestler, S.J. Park, R.C. Daly, K.L. Greason, J. Jen, L.Q. Wu, W.F. Shen, W.K. Shen, Y.M. Cha, H.C. Lee, Regulation of the SK3 channel by microRNA-499--potential role in atrial fibrillation. Heart. Rhythm. 10(7), 1001–1009 (2013)PubMedCentralCrossRefGoogle Scholar
- 25.European Heart Rhythm, A., European Association for Cardio-Thoracic, S., A.J. Camm, P. Kirchhof, G.Y. Lip, U. Schotten, I. Savelieva, S. Ernst, I.C. Van Gelder, N. Al-Attar, G. Hindricks, B. Prendergast, H. Heidbuchel, O. Alfieri, A. Angelini, D. Atar, P. Colonna, R. De Caterina, J. De Sutter, A. Goette, B. Gorenek, M. Heldal, S.H. Hohloser, P. Kolh, J.Y. Le Heuzey, P. Ponikowski, F.H. Rutten, Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur. Heart. J. 31(19), 2369–2429 (2010)CrossRefGoogle Scholar
- 26.N. Hakimzadeh, A.Y. Nossent, A.M. van der Laan, S.H. Schirmer, M.W. de Ronde, S.J. Pinto-Sietsma, N. van Royen, P.H. Quax, I.E. Hoefer, J.J. Piek, Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function. PLoS ONE 10(9), e0137035 (2015)PubMedCentralCrossRefGoogle Scholar
- 29.X. Zhang, S. Shao, H. Geng, Y. Yu, C. Wang, Z. Liu, C. Yu, X. Jiang, Y. Deng, L. Gao, J. Zhao, Expression profiles of six circulating microRNAs critical to atherosclerosis in patients with subclinical hypothyroidism: a clinical study. J. Clin. Endocrinol. Metab. 99(5), E766–E774 (2014)CrossRefGoogle Scholar
- 32.L. Jiang, J. Huang, Y. Chen, Y. Yang, R. Li, Y. Li, X. Chen, D. Yang, Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome. Endocrine 53(1), 280–290 (2016)CrossRefGoogle Scholar
- 35.D.D. McManus, K. Tanriverdi, H. Lin, N. Esa, M. Kinno, D. Mandapati, S. Tam, O.N. Okike, P.T. Ellinor, J.F. Keaney Jr., J.K. Donahue, E.J. Benjamin, J.E. Freedman, Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study). Heart. Rhythm. 12(1), 3–10 (2015)CrossRefGoogle Scholar
- 42.P.K. Rao, Y. Toyama, H.R. Chiang, S. Gupta, M. Bauer, R. Medvid, F. Reinhardt, R. Liao, M. Krieger, R. Jaenisch, H.F. Lodish, R. Blelloch, Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure. Circ. Res. 105(6), 585–594 (2009)PubMedCentralCrossRefGoogle Scholar
- 43.D. Terentyev, A.E. Belevych, R. Terentyeva, M.M. Martin, G.E. Malana, D.E. Kuhn, M. Abdellatif, D.S. Feldman, T.S. Elton, S. Gyorke, miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2. Circ. Res. 104(4), 514–521 (2009)PubMedCentralCrossRefGoogle Scholar
- 46.X. Jia, S. Zheng, X. Xie, Y. Zhang, W. Wang, Z. Wang, Y. Zhang, J. Wang, M. Gao, Y. Hou, MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model. PLoS ONE 8(12), e85639 (2013)PubMedCentralCrossRefGoogle Scholar
- 49.Y.D. Li, Y.F. Hong, Y. Yusufuaji, B.P. Tang, X.H. Zhou, G.J. Xu, J.X. Li, L. Sun, J.H. Zhang, Q. Xin, J. Xiong, Y.T. Ji, Y. Zhang, Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation. Mol. Med. Rep. 12(3), 3243–3248 (2015)PubMedCentralCrossRefGoogle Scholar