Increased Otolin-1 in Serum as a Potential Biomarker for Idiopathic Benign Paroxysmal Positional Vertigo Episodes

Yunqin Wu, Weiwei Han, Wang Yan, Xiaoxiong Lu, Min Zhou, Li Li, Qiongfeng Guan, Zhenyi Fan, Yunqin Wu, Weiwei Han, Wang Yan, Xiaoxiong Lu, Min Zhou, Li Li, Qiongfeng Guan, Zhenyi Fan

Abstract

Objective: Otolin-1, a main specific otoconia matrix protein, passes through the labyrinth-blood barrier and is detectable in peripheral blood. Serum otolin-1 levels differ between patients with benign paroxysmal positional vertigo (BPPV) and healthy controls and are significantly age-related, increasing in healthy controls with age, suggesting that serum otolin-1 levels reflect otolith status. The aim of this study was to determine whether otolin-1 levels change during vertigo episodes in patients with BPPV and whether any change is specific and sensitive enough for BPPV episodes. Method: Patients diagnosed with de novo idiopathic BPPV during an acute episode were included in the study from May 2017 to May 2018. Blood samples were drawn before patients were treated with canalith-repositioning maneuvers. Serum otolin-1 levels were compared between 78 patients and 121 age- and sex-matched healthy individuals. Results: There were no significant differences between the groups in the age distribution, sex ratio, body mass index, clinical history, routine blood parameters, or total protein, albumin, uric acid, creatinine, blood urea nitrogen and lipid profiles (P > 0.05). Serum levels of otolin-1 were significantly higher in BPPV patients than in healthy controls (P < 0.001). Receiver operating characteristic analysis revealed that a serum otolin-1 value of 299.45 pg/ml was the optimal cut-off value to discriminate patients with BPPV from healthy controls (area under the curve 0.757, 95% CI 0.687~0.826) with a sensitivity of 67.9% and a specificity of 72.7%. Conclusion: Serum levels of otolin-1 may be a potential biomarker for BPPV episodes.

Keywords: benign paroxysmal positional vertigo; biomarker; otoconia; otolin-1; vertigo.

Copyright © 2020 Wu, Han, Yan, Lu, Zhou, Li, Guan and Fan.

Figures

Figure 1
Figure 1
Serum concentrations of otolin-1 in subjects with BPPV and healthy controls.
Figure 2
Figure 2
Comparison of serum otolin-1 levels in subjects with BPPV and healthy controls.
Figure 3
Figure 3
Serum otolin-1 levels provided an area under the curve of 0.757, 95% CI (0.687~0.826) (sensitivity = 67.9%, specificity = 72.7%) for BPPV patients vs. healthy controls.

References

    1. Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery Guideline of diagnosis and treatment of benign paroxysmal positional vertigo (in Chinese). Chin J Otorhinolaryngol Head Neck Surg. (2017) 52:173–7. 10.3760/cma.j.issn.1673-0860.2017.03.003
    1. Wu Y, Fan Z, Jin H, Guan Q, Zhou M, Lu X, et al. . Assessment of bone metabolism in male patients with benign paroxysmal positional vertigo. Front Neurol. (2018) 9:742. 10.3389/fneur.2018.00742
    1. von Brevern M, Bertholon P, Brandt T, Fife T, Imai T, Nuti D, et al. . Benign paroxysmal positional vertigo: diagnostic criteria consensus document of the committee for the classification of vestibular disorders of the BáránySociety. Acta Otorrinolaringol Esp. (2017) 68:349–60. 10.1016/j.otorri.2017.02.007
    1. Kim JS, Zee DS. Benign paroxysmal positioning vertigo. N Engl J Med. (2014) 370:1138–47. 10.1056/NEJMcp1309481
    1. Jahn K, Langhagen T, Heinen F. Vertigo and dizziness in children. Curr Opin Neurol. (2015) 28:78–82. 10.1097/WCO.0000000000000157
    1. Mandalà M, Salerni L, Nuti D. Benign positional paroxysmal vertigo treatment: a practical update. Curr Treat Options Neurol. (2019) 21:66. 10.1007/s11940-019-0606-x
    1. Walther LE, Wenzel A, Buder J, Bloching MB, Kniep R, Blodow A. Detection of human utricularotoconia degeneration in vital specimen and implications for benign paroxysmal positional vertigo. Eur Arch Otorhinolaryngol. (2013) 271:3133–8. 10.1007/s00405-013-2784-6
    1. Hołubowicz R, Wojtas M, Taube M, Kozak M, Ozyhar A, Dobryszycki P. Effect of calcium ions on structure and stability of the C1q-like domain of otolin-1 from human and zebrafish. FEBS J. (2017) 284:4278–97. 10.1111/febs.14308
    1. Lunderg YW, Xu Y, Thiessen KD, Kramer KL. Mechanisms of otoconia and otolith development. Dev Dyn. (2015) 244:239–53. 10.1002/dvdy.24195
    1. Moreland KT, Hong M, Lu W, Rowley CW, Ornitz DM, de Yoreo JJ, et al. . In vitro calcite crystal morphology is modulated by otoconial proteins otolin-1 and otoconin-90. PLoS ONE. (2014) 9:e95333. 10.1371/journal.pone.0095333
    1. Deans MR, Peterson JM, Wong GW. Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1. PLoS ONE. (2010) 5:e12765. 10.1371/journal.pone.0012765
    1. Kawamata S, Igarashi Y. Growth and turnover of rat otoconia as revealed by labeling with tetracycline. Anat Rec. (1995) 242:259–66. 10.1002/ar.1092420216
    1. Xu Y, Zhang Y, Lundberg YW. Spatiotemporal differences in otoconial gene expression. Genesis. (2016) 54:613–25. 10.1002/dvg.22990
    1. Takumida M, Zhang DM, Yajin K, Harada Y. Formation and fate of giant otoconia of the guinea pig following streptomycin intoxication. Acta Otolaryngol. (1997) 117:538–44. 10.3109/00016489709113434
    1. Zucca G, ValliS Valli P, Perin P, Mira E. Why do benign paroxysmal positional vertigo episodes recover spontaneously? J Vestib Res. (1998) 8:325–9. 10.3233/VES-1998-8404
    1. Mulry E, Parham K. Inner ear proteins as potential biomarkers. Otol Neurotol. (2020) 41:145–52. 10.1097/MAO.0000000000002466
    1. Marchler-Bauer A, Bo Y, Han L, He J, Lanczycki CJ, Lu S, et al. . CDD/SPARCLE: functional classification of proteins via subfamily domain architectures. Nucleic Acids Res. (2017) 45:D200–D203. 10.1093/nar/gkw1129
    1. Parham K, Sacks D, Bixby C, Fall P. Inner ear protein as a bio marker in circulation? Otolaryngol Head Neck Surg. (2014) 151:1038–40. 10.1177/0194599814551127
    1. Tabtabai R, Haynes L, Kuchel GA, Parham K. Age-related increase in blood levels of Otolin-1 in humans. Otol Neurotol. (2017) 38:865–9. 10.1097/MAO.0000000000001426
    1. Jang YS, Hwang CH, Shin JY, Bae WY, Kim LS. Age-related changes on the morphology of the otoconia. Laryngo Scope. (2006) 116:996–1001. 10.1097/01.mlg.0000217238.84401.03
    1. Vibert D, Sans A, Kompis M, Travo C, Muhlbauer RC, Tschudi I, et al. . Ultrastructural changes in otoconia of osteoporotic rats. Audiol Neuro Otol. (2008) 13:293–301. 10.1159/000124277
    1. Li JC, Li CJ, Epley J, Weinberg L. Cost-effective management of benign positional vertigo using canalith repositioning. Otolaryngol Head Neck Surg. (2000) 122:334–9. 10.1067/mhn.2000.100752
    1. Qian SX, Li F, Zhuang JH, Chen Y, Yang HL, Zhou XW, et al. Misdiagnosis and associated costs of benign paroxysmal positional vertigo(in Chinese). Chin Med J. (2017) 7:1057–60. 10.3760/cma.j.issn.0376-2491.2017.14.006
    1. Wang YL, Wu MY, Cheng PL, Pei SF, Liu Y, Liu YM. Analysis of cost and effectiveness of treatment in benign paroxysmal positional vertigo. Chin Med J. (2017) 132:342–5. 10.1097/CM9.0000000000000063
    1. Ozbay I, Kahraman C, Balikc HH, Kucur C, Kahraman NK, Ozkaya DP, et al. . Neutrophil-to-lymphocyte ratio in patients with peripheral vertigo. A prospective controlled clinical study. Am J Otolaryngol. (2014) 35:699–702. 10.1016/j.amjoto.2014.08.004
    1. Han W, Fan Z, Zhou M, Guo X, Yan W, Lu X, et al. . Low 25-hydroxyvitamin D levels in postmenopausal female patients with benign paroxysmal positional vertigo. Acta Otolaryngol. (2018) 138:443–6. 10.1080/00016489.2017.1416168
    1. Akinci E, Aygencel G, Keles A, Demircan A, Bildik F. Role of C-reactive protein, D-dimer, and fibrinogen levels in the differential diagnosis of central and peripheral vertigo. Adv Ther. (2007) 24:1068–77. 10.1007/BF02877713
    1. Yang X, Yang B, Wu M, Wang F, Huang X, Li K, et al. . Association between serum uric acid levels and benign paroxysmal positional vertigo: a systematic review and meta-analysis of observational studies. Front Neurol. (2019) 10:91. 10.3389/fneur.2019.00091
    1. Rödöö P, Hellberg D. Creatine kinase MB (CK-MB) in benign paroxysmal vertigo of childhood: a new diagnostic marker. J Pediatr. (2005) 146:548–51. 10.1016/j.jpeds.2004.10.062
    1. Torun MT, Yalçin Y, ÖzkanÖ. Can CK-MB be used as a marker in benign paroxysmal positional vertigo attack? Int Tinnitus J. (2017) 20:69–72. 10.5935/0946-5448.20160013
    1. Wu Y, Gu C, Han W, Lu X, Chen C, Fan Z. Reduction of bone mineral density in native Chinese female idiopathic benign paroxysmal positional vertigo patients. Am J Otolaryngol. (2018) 39:31–3. 10.1016/j.amjoto.2017.09.004
    1. Shim DB, Ko KM, Lee JH, Park HJ, Song MH. Natural history of horizontal canal benign paroxysmal positional vertigo is truly short. J Neurol. (2015) 262:74–80. 10.1007/s00415-014-7519-0
    1. Murat D, Mustafa S, Yusuf K. Otolin-1, as a potential marker for inner ear trauma after mastoidectomy. J Int Adv Otol. (2019) 15:200–3. 10.5152/iao.2019.5155

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