Advertisement

The serum YKL-40 level is a potential biomarker for OSAHS: a systematic review and meta-analysis

  • Yan Zhang
  • Xiaoli SuEmail author
  • Pinhua Pan
  • Chengping Hu
Sleep Breathing Physiology and Disorders • Original Article
  • 17 Downloads

Abstract

Purpose

Several studies have reported that serum YKL-40 level was elevated in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, most of these studies had relatively small sample sizes and the results were inconsistent. Therefore, a meta-analysis was conducted to determine the potential role of serum YKL-40 level in OSAHS.

Methods

A systematic literature search was performed in several databases to identify eligible studies involving the relationship between serum YKL-40 level and OSAHS. The standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated to determine the effect sizes.

Results

Five eligible articles were extracted in this meta-analysis. The pooled results demonstrated that the serum YKL-40 level was significantly higher in OSAHS patients compared with their non-OSAHS controls (SMD 1.03, 95% CI 0.46, 1.59, I2 = 87%, P = 0.0004). The subgroup analysis showed that Asian (SMD 1.81, 95% CI 1.41, 2.21, I2 = 0%, P < 0.00001) and Caucasian (SMD 0.67, 95% CI 0.39, 0.96, I2 = 0%, P < 0.00001) patients with OSAHS had higher serum YKL-40 levels than their non-OSAHS controls. YKL-40 level in serum was increased in OSAHS patients with BMI < 28 (SMD 1.81, 95% CI 1.41, 2.21, I2 = 0%, P < 0.00001), as well as in patients with BMI ≥ 28 (SMD 0.57, 95% CI 0.33, 0.81, I2 = 0%, P < 0.00001). In addition, OSAHS patients with cardiac complications had a higher serum YKL-40 level compared with those patients without cardiac complications (SMD 0.80, 95% CI 0.32, 1.28, I2 = 67%, P = 0.001).

Conclusions

This study indicates that OSAHS patients have higher serum YKL-40 level, which may serve as a potential biomarker for OSAHS diagnosis and monitoring.

Keywords

YKL-40 OSAHS Biomarker Meta-analysis 

Notes

Acknowledgments

We really thank Karan Sachdeva, a medical student in Maulana Azad Medical College in India, for helping to polish the language.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Caples SM, Gami AS, Somers VK (2005) Obstructive sleep apnea. Ann Intern Med 142(3):187–197CrossRefGoogle Scholar
  2. 2.
    Punjabi NM (2008) The epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc 5(2):136–143CrossRefGoogle Scholar
  3. 3.
    Kokturk O, Ciftci TU, Mollarecep E, Ciftci B (2005) Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome. Int Heart J 46(5):801–809CrossRefGoogle Scholar
  4. 4.
    Al Lawati N, Mulgrew A, Cheema R, vanEeden S, Butt A, Fleetham J, Ryan F, Ayas N (2009) Pro-atherogenic cytokine profile of patients with suspected obstructive sleep apnea. Sleep Breath 13(4):391–395CrossRefGoogle Scholar
  5. 5.
    Htoo AK, Greenberg H, Tongia S, Chen G, Henderson T, Wilson D, Liu SF (2006) Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath 10(1):43–50CrossRefGoogle Scholar
  6. 6.
    Yamauchi M, Tamaki S, Tomoda K, Yoshikawa M, Fukuoka A, Makinodan K, Koyama N, Suzuki T, Kimura H (2006) Evidence for activation of nuclear factor kappaB in obstructive sleep apnea. Sleep Breath 10(4):189–193CrossRefGoogle Scholar
  7. 7.
    Nadeem R, Molnar J, Madbouly EM, Nida M, Aggarwal S, Sajid H, Naseem J, Loomba R (2013) Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med 9(10):1003–1012Google Scholar
  8. 8.
    Rathcke CN, Vestergaard H (2009) YKL-40- an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol 8:61CrossRefGoogle Scholar
  9. 9.
    El Basha NR, Osman HM, Abdelaal AA, Saed SM, Shaaban HH (2018) Increased expression of serum periostin and YKL40 in children with severe asthma and asthma exacerbation. J Investig Med 66(8):1102–1108CrossRefGoogle Scholar
  10. 10.
    Väänänen T, Vuolteenaho K, Kautiainen H, Nieminen R, Möttönen T, Hannonen P, Korpela M, Kauppi MJ, Laiho K, Kaipiainen-Seppänen O, Luosujärvi R, Uusitalo T, Uutela T, Leirisalo-Repo M, Moilanen E, NEO-RACo Study Group (2017) Glycoprotein YKL-40: a potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial. PLoS One 12(8):e0183294CrossRefGoogle Scholar
  11. 11.
    Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H (2009) YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 32(2):323–328CrossRefGoogle Scholar
  12. 12.
    Erzin Y, Uzun H, Karatas A, Celik AF (2008) Serum YKL-40 as a marker of disease activity and stricture formation in patients with Crohn’s disease. J Gastroenterol Hepatol 23:e357–e362CrossRefGoogle Scholar
  13. 13.
    Bilim O, Takeishi Y, Kitahara T, Ishino M, Sasaki T, Suzuki S, Shishido T, Kubota I (2010) Serum YKL-40 predicts adverse clinical outcomes in patients with chronic heart failure. J Card Fail 16(11):873–879CrossRefGoogle Scholar
  14. 14.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8(5):336–341CrossRefGoogle Scholar
  15. 15.
    Borenstein M, Hedges L, Rothstein H (2007) Meta-analysis: fixed effect vs. random effects. Available from: Meta-analysis.com. Accessed June 17, 2017
  16. 16.
    Mutlu LC, Tülübaş F, Alp R, Kaplan G, Yildiz ZD, Gürel A (2017) Serum YKL-40 level is correlated with apnea hypopnea index in patients with obstructive sleep apnea sindrome. Eur Rev Med Pharmacol Sci 21(18):4161–4166Google Scholar
  17. 17.
    Jafari B, Mohsenin V (2016) Chitinase-3-like protein-1 (YKL-40) as a marker of endothelial dysfunction in obstructive sleep apnea. Sleep Med 25:87–92CrossRefGoogle Scholar
  18. 18.
    Bakırcı EM, Ünver E, Değirmenci H, Kıvanç T, Günay M, Hamur H, Büyüklü M, Ceyhun G, Topal E, Çoban TA (2015) Serum YKL-40/chitinase 3-like protein 1 level is an independent predictor of atherosclerosis development in patients with obstructive sleep apnea syndrome. Turk Kardiyol Dern Ars 43(4):333–339Google Scholar
  19. 19.
    Hang YP, Xiao YL, Zhang DP, Cai HR (2011) Changes of serum levels of YKL-40 in patients with obstructive sleep apnea hypopnea syndrome and its clinical significance. Journal of Clinical Pulmonary Medicine 16(6):857–858Google Scholar
  20. 20.
    Li K, Chen Z, Qin Y, Wei YX (2019) Plasm YKL-40 levels are associated with hypertension in patients with obstructive sleep apnea. Biomed Res Int 13:5193597Google Scholar
  21. 21.
    Bara I, Ozier A, Girodet PO, Carvalho G, Cattiaux J, Begueret H, Thumerel M, Ousova O, Kolbeck R, Coyle AJ, Woods J, Tunon de Lara JM, Marthan R, Berger P (2012) Role of YKL-40 in bronchial smooth muscle remodeling in asthma. Am J Respir Crit Care Med 185(7):715–722CrossRefGoogle Scholar
  22. 22.
    Francescone RA, Scully S, Falbish M, Taylor SL, Oh D, Moral L, Yan W, Bentley B, Shao R (2011) Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J Biol Chem 286(17):15332–15343CrossRefGoogle Scholar
  23. 23.
    Li W, Yu Z, Jiang C (2014) Association of serum YKL-40 with the presence and severity of obstructive sleep apnea syndrome. Lab Med 45(3):220–225CrossRefGoogle Scholar
  24. 24.
    Duru S, Yüce G, Fırat H, Şimşek B, Uçar F, Ardıç S, Kurt EB (2015) YKL-40: may be use as a new inflammatory biomarker in obstructive sleep apnea syndrome? Tuberk Toraks 63(3):158–164CrossRefGoogle Scholar
  25. 25.
    Wang X, Xing GH (2014) Serum YKL-40 concentrations are elevated and correlated with disease severity in patients with obstructive sleep apnea syndrome. Scand J Clin Lab Invest 74(1):74–78CrossRefGoogle Scholar
  26. 26.
    Gumus A, Kayhan S, Cinarka H, Kirbas A, Bulmus N, Yavuz A, Sahin U, Ozkaya S (2013) High serum YKL-40 level in patients with COPD is related to hypoxemia and disease severity. Tohoku J Exp Med 229:163–170CrossRefGoogle Scholar
  27. 27.
    Weiss JW, Launois SH, Anand A, Garpestad E (1999) Cardiovascular morbidity in obstructive sleep apnea. Prog Cardiovasc Dis 41(5):367–376CrossRefGoogle Scholar
  28. 28.
    Harutyunyan M, Gotze JP, Winkel P, Johansen JS, Hansen JF, Jensen GB, Hilden J, Kjøller E, Kolmos HJ, Gluud C, Kastrup J (2013) Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: a prognostic study within the CLARICOR trial. Immunobiology 218(7):945–951CrossRefGoogle Scholar
  29. 29.
    Kastrup J, Johansen JS, Winkel P, Hansen JF, Hildebrandt P, Jensen GB, Jespersen CM, Kjøller E, Kolmos HJ, Lind I, Nielsen H, Gluud C, CLARICOR Trial Group (2009) High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease. Eur Heart J 30(9):1066–1072CrossRefGoogle Scholar
  30. 30.
    Harutyunyan M, Christiansen M, Johansen JS, Kober L, Torp-Petersen C, Kastrup J (2012) The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure. Immunobiology 217(6):652–656CrossRefGoogle Scholar
  31. 31.
    Jafari B, Elias JA, Mohsenin V (2014) Increased plasma YKL-40/chitinase-3-like-protein-1 is associated with endothelial dysfunction in obstructive sleep apnea. PLoS One 9(5):e98629CrossRefGoogle Scholar
  32. 32.
    Reutrakul S, Mokhlesi B (2017) Obstructive sleep apnea and diabetes: a state of the art review. Chest 152(5):1070–1086CrossRefGoogle Scholar
  33. 33.
    Sun L, Liu JY, Li LR (2015) Serum YKL-40 levels are associated with type 2 diabetes mellitus in patients with obstructive sleep apnea syndrome. Genet Mol Res 14(3):8919–8925CrossRefGoogle Scholar
  34. 34.
    Rathcke CN, Johansen JS, Vestergaard H (2006) YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance. Inflamm Res 55(2):53–59CrossRefGoogle Scholar
  35. 35.
    Teitsdottir UD, Arnardottir ES, Bjornsdottir E, Gislason T, Petersen PH (2018) Obesity modulates the association between sleep apnea treatment and CHI3L1 levels but not CHIT1 activity in moderate to severe OSA: an observational study. Sleep Breath 22(4):1101–1109CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yan Zhang
    • 1
  • Xiaoli Su
    • 1
    Email author
  • Pinhua Pan
    • 1
  • Chengping Hu
    • 1
  1. 1.Department of Respiratory Medicine, Xiangya Hospital (Key Cite of National Clinical Research Center for Respiratory Disease)Central South UniversityChangshaChina

Personalised recommendations