The relationship between NLRP3 rs10159239 and Vaspin rs2236242 gene variants and obstructive sleep apnea

DOI: https://doi.org/10.48101/ujms.v126.7603
Keywords: Obstructive sleep apnea, polymorphism, vaspin, NLRP3, Elisa

Abstract

Background: In obstructive sleep apnea (OSA), recurrent upper airway obstruction and apnea/hypopnea episodes result in endothelial dysfunction, which leads to the release of many proinflammatory cytokines and reactive oxygen species (ROS). ROS induces NLRP3, a protein involved in the synthesis of interleukin (IL)-1 and IL-18; vaspin is a serine protease inhibitor that has an important role in suppressing the activation of NLRP3 inflammasome. In this study, we aimed to investigate the effect of NLRP3 rs10159239 (rs9239) and vaspin rs2236242 (rs6242) single nucleotide polymorphisms (SNPs) on OSA development.

Methods: This study included 220 individuals who underwent polysomnography (118 patients with OSA and 102 healthy controls). NLRP3 rs9239 and vaspin rs6242 mutation frequencies were analyzed.

Results: The NLRP3 rs9239 SNP genotype analysis revealed no statistically significant differences between the OSA and control groups. In the vaspin gene analysis, the rs6242 AA genotype was significantly more frequent in the OSA group compared with the control group, while the AT genotype was more frequent in controls (P = 0.004, P = 0.02). Comparison of rs6242 allele levels showed that the A allele was significantly more frequent in OSA patients than in controls (P = 0.03). The AA genotype was significantly more frequent in patients with severe OSA than in patients with mild or moderate OSA and the control group (P = 0.001 for all). Serum vaspin levels were significantly lower in carriers of the AA genotype than those with AT and TT genotypes (P = 0.001).

Conclusion: The vaspin rs6242 SNP AA genotype increased susceptibility to OSA, while the AT genotype appeared to be protective. The lower plasma vaspin levels in OSA compared with the control group and in patients with the AA genotype suggest that vaspin may be a protective biomarker for OSA.

Downloads

Download data is not yet available.

References


  1. Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13:479–504. doi: 10.5664/jcsm.6506

  2. Bhushan B, Guleria R, Misra A, Luthra K, Vikram NK. TNF-alpha gene polymorphism and TNF-alpha levels in obese Asian Indians with obstructive sleep apnea. Respir Med. 2009;103:386–92. doi: 10.1016/j.rmed.2008.10.001

  3. Ip MS, Lam KS, Ho C-M, Tsang KW, Lam W-K. Serum leptin and vascular risk factors in obstructive sleep apnea. Chest. 2000;118:580–6. doi: 10.1378/chest.118.3.580

  4. Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia–revisited–the bad ugly and good: implications to the heart and brain. Sleep Med Rev. 2015;20:27–45. doi: 10.1016/j.smrv.2014.07.003

  5. McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med. 2009;180:692–700. doi: 10.1164/rccm.200903-0347PP

  6. Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10:210–15. doi: 10.1038/nri2725

  7. Tang T, Huang Q, Liu J, Zhou X, Du J, Wu H, et al. Oxidative stress does not contribute to the release of proinflammatory cytokines through activating the nod-like receptor protein 3 inflammasome in patients with obstructive sleep apnoea. Sleep Breathing. 2019;23:535–42. doi: 10.1007/s11325-018-1726-3

  8. Akosile W, Voisey J, Lawford B, Colquhoun D, Young RM, Mehta D, et al. NLRP3 is associated with coronary artery disease in Vietnam veterans. Gene. 2020;725:144163. doi: 10.1016/j.gene.2019.144163

  9. Ding S, Xu S, Ma Y, Liu G, Jang H, Fang J. Modulatory mechanisms of the NLRP3 inflammasomes in diabetes. Biomolecules. 2019;9:850. doi: 10.3390/biom9120850

  10. Trujillo ME, Scherer PE. Adipose tissue-derived factors: impact on health and disease. Endocrine Rev. 2006;27:762–78. doi: 10.1210/er.2006-0033

  11. Li K, Li L, Yang M, Liu H, Liu D, Yang H, et al. Short-term continuous subcutaneous insulin infusion decreases the plasma vaspin levels in patients with type 2 diabetes mellitus concomitant with improvement in insulin sensitivity. Eur J Endocrinol. 2011;164:905. doi: 10.1530/EJE-10-1023

  12. Kiskac M, Zorlu M, Akkoyunlu ME, Kilic E, Karatoprak C, Cakirca M, et al. Vaspin and lipocalin-2 levels in severe obsructive sleep apnea. J Thoracic Dis. 2014;6:720.

  13. Li J, Li Q, Zhu YC, Wang YK, Gao CP, Li XY, et al. Association of vaspin rs2236242 gene variants with type 2 diabetes and obesity in a Chinese population: a prospective, single‐center study. J Cell Physiol. 2019;234:16097–101. doi: 10.1002/jcp.28267

  14. Akcılar R, Yümün G, Bayat Z, Donbaloğlu O, Gür Ö, Gürkan S, et al. Association of vaspin rs2236242 gene variants and circulating serum vaspin concentrations with coronary artery disease in a Turkish population. J Cell Physiol. 2020;236:3734–9. doi: 10.1002/jcp.30112

  15. Ryckman K, Williams SM. Calculation and use of the Hardy‐Weinberg model in association studies. Curr Protocols Hum Genet. 2008;57:1.18.1–1.. 1. doi: 10.1002/0471142905.hg0118s57

  16. Guilleminault C. City and morbidity of obstructive sleep apnea syndrome. Prospective studies on retrospective cohorts. Sleep Breathing. 1994;71:557–75.

  17. Lavie L. Obstructive sleep apnoea syndrome–an oxidative stress disorder. Sleep Med Rev. 2003;7:35–51. doi: 10.1053/smrv.2002.0261

  18. Malhotra A, White DP. Obstructive sleep apnoea. Lancet. 2002;360:237–45. doi: 10.1016/S0140-6736(02)09464-3

  19. Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003;290:1906–14. doi: 10.1001/jama.290.14.1906

  20. Kerget B, Afşin DE, Kerget F, Aşkın S, Araz Ö, Akgün M. Is vimentin the cause or effect of obstructive sleep apnea development? Lung. 2020;157:1–8. doi: 10.1016/j.chest.2020.05.364

  21. Ciftci TU, Kokturk O, Bukan N, Bilgihan A. The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome. Cytokine. 2004;28:87–91. doi: 10.1016/j.cyto.2004.07.003

  22. Liu H, Lin M, Guan P, Xu Y. The change of platelet derived growth factor in patients with obstructive sleep apnea-hypopnea syndrome. Zhonghua jie he he hu xi za zhi= Zhonghua jiehe he huxi zazhi= Chin J Tuberc Respir Dis. 2006;29:536–40.

  23. Araz O, Ucar EY, Dorman E, Bayraktutan Z, Yayla M, Yilmaz N, et al. Is there a relationship between obstructive sleep apnea syndrome severity and nesfatin-1? Respiration. 2015;90:105–10. doi: 10.1159/000431180

  24. De SS, Cambi J, Tatti P, Bellussi L, Passali D. Changes in ghrelin, leptin and pro-inflammatory cytokines after therapy in Obstructive Sleep Apnea Syndrome (OSAS) patients. Otolaryngologia polska= Polish Otolaryngol. 2015;69:1–8. doi: 10.5604/00306657.1147029

  25. Liu W, Yin Y, Zhou Z, He M, Dai Y. OxLDL-induced IL-1beta secretion promoting foam cells formation was mainly via CD36 mediated ROS production leading to NLRP3 inflammasome activation. Inflamm Res. 2014;63:33–43. doi: 10.1007/s00011-013-0667-3

  26. Wang H, Wang S, Ying H, Weng Y, Yu W. NLRP3 inflammasome involves in the acute exacerbation of patients with chronic obstructive pulmonary disease. Inflammation. 2018;41:1321–33. doi: 10.1007/s10753-018-0780-0

  27. Lasithiotaki I, Giannarakis I, Tsitoura E, Samara KD, Margaritopoulos GA, Choulaki C, et al. NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung. Eur Respir J. 2016;47:910–18. doi: 10.1183/13993003.00564-2015

  28. Li X, Ke X, Li Z, Li B. Vaspin prevents myocardial injury in rats model of diabetic cardiomyopathy by enhancing autophagy and inhibiting inflammation. Biochem Biophys Res Commun. 2019;514:1–8. doi: 10.1016/j.bbrc.2019.04.110

  29. Ghany SMA, Sayed AA, El-Deek SE, ElBadre HM, Dahpy MA, Saleh MA, et al. Obesity risk prediction among women of Upper Egypt: the impact of serum vaspin and vaspin rs2236242 gene polymorphism. Gene. 2017;626:140–8. doi: 10.1016/j.gene.2017.05.007

Published
2021-06-02
How to Cite
Kerget B., Kerget F., Yüce Kahraman Çiğdem, Aksakal A., & Araz Ömer. (2021). The relationship between NLRP3 rs10159239 and Vaspin rs2236242 gene variants and obstructive sleep apnea. Upsala Journal of Medical Sciences, 126(1). https://doi.org/10.48101/ujms.v126.7603
Issue
Vol. 126 (2021): Upsala J Med Sci
Section
Original Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors retain copyright of their work, with first publication rights granted to Upsala Medical Society. Read the full Copyright- and Licensing Statement.

Crossref
Scopus
Google Scholar
Europe PMC