Serum cfDNA and TNF-α in Adult Men with Obstructive Sleep Apnea

ORIGINAL ARTICLE
Waheeb Alharbi, Ahmad H. Mufti

 
For citation: Alharbi W, Mufti AH. Serum cfDNA and TNF-α in Adult Men with Obstructive Sleep Apnea. International Journal of Biomedicine. 2026;16(2):217-222. doi:10.21103/Article16(2)_OA10
 
Originally published June 5, 2026

Abstract: 

Background: Obstructive sleep apnea (OSA) is a common sleep-related chronic respiratory disorder. There are several factors for characterizing OSA in adults. Two of the potential biomarkers in OSA are cell-free DNA (cfDNA) and tumor necrosis factor-alpha (TNF-α). Some reports indicate that obesity and other variables are likely the major risk factors influencing changes in serum cfDNA and TNF-α levels. Given the controversial role of these two biomarkers, we planned to conduct the present study in male patients with mild OSA and normal body mass index (BMI).
Methods and Results: Two groups of subjects were examined. Group 1 included 195 OSA men. Group 2 included 201 men as normal controls (NC) without OSA. The participants in both groups were aged 51-60 years and had normal BMI in the range of 18.5 to 24.9 kg/m2. Polysomnography was used to determine the apnea-hypopnea index (AHI) and assess the severity of OSA. The routine ELISA method was used to assess TNF-α and cfDNA in blood serum.
The present report found a significant increase in serum levels of cfDNA and TNF-α in OSA men with normal BMI compared to healthy control men with normal BMI. Still, we did not find a significant correlation between serum cfDNA and TNF-α in the NC and OSA groups.
Conclusion: The role of significantly increased levels of serum cfDNA and TNF-α is evident in OSA men with normal weight BMI. Though both cfDNA and TNF-α show a significant correlation with BMI in obese patients with OSA, a direct association between cfDNA and TNF-α in normal-weight men with OSA is not evident. Future studies examining the involvement of key pro-inflammatory and anti-inflammatory biomarkers will clarify the precise roles of serum cfDNA and TNF-α in patients with OSA.

Keywords: 
obstructive sleep apnea • TNF-α • cfDNA • BMI • adult men
References: 
  1. Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, Mooser V, Preisig M, Malhotra A, Waeber G, Vollenweider P, Tafti M, Haba-Rubio J. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015 Apr;3(4):310-8. doi: 10.1016/S2213-2600(15)00043-0. Epub 2015 Feb 12. PMID: 25682233; PMCID: PMC4404207.
  2. Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O'Connor GT, Rapoport DM, Redline S, Resnick HE, Robbins JA, Shahar E, Unruh ML, Samet JM. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med. 2009 Aug;6(8):e1000132. doi: 10.1371/journal.pmed.1000132. Epub 2009 Aug 18. PMID: 19688045; PMCID: PMC2722083.
  3. Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004 Apr 28;291(16):2013-6. doi: 10.1001/jama.291.16.2013. PMID: 15113821.
  4. Mediano O, Cano-Pumarega I, Sánchez-de-la-Torre M, Alonso-Álvarez ML, Troncoso MF, García-Río F, Egea C; Spanish Sleep Network; Spanish Sleep Network. Upcoming Scenarios for the Comprehensive Management of Obstructive Sleep Apnea: An Overview of the Spanish Sleep Network. Arch Bronconeumol (Engl Ed). 2020 Jan;56(1):35-41. English, Spanish. doi: 10.1016/j.arbres.2019.05.017. Epub 2019 Aug 5. PMID: 31395388.
  5. Li D, Kuang B, Lobbezoo F, de Vries N, Hilgevoord A, Aarab G. Sleep bruxism is highly prevalent in adults with obstructive sleep apnea: a large-scale polysomnographic study. J Clin Sleep Med. 2023 Mar 1;19(3):443-451. doi: 10.5664/jcsm.10348. PMID: 36448332; PMCID: PMC9978428.
  6. Patel SR. Entering a New Era in Sleep-Apnea Treatment. N Engl J Med. 2024 Oct 3;391(13):1248-1249. doi: 10.1056/NEJMe2407117. Epub 2024 Jun 21. PMID: 38912659.
  7. Lal C, Weaver TE, Bae CJ, Strohl KP. Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management. Ann Am Thorac Soc. 2021 May;18(5):757-768. doi: 10.1513/AnnalsATS.202006-696FR. PMID: 33621163; PMCID: PMC8086534.
  8. Chen X, Wang R, Zee P, Lutsey PL, Javaheri S, Alcántara C, Jackson CL, Williams MA, Redline S. Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015 Jun 1;38(6):877-88. doi: 10.5665/sleep.4732. PMID: 25409106; PMCID: PMC4434554.
  9. Chinese Thoracic Society. [Expert consensus on the diagnosis and treatment of obstructive sleep apnea in women]. Zhonghua Jie He He Hu Xi Za Zhi. 2024 Jun 12;47(6):509-528. Chinese. doi: 10.3760/cma.j.cn112147-20240206-00072. PMID: 38858201.
  10. Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Matheson MC, Hamilton GS, Dharmage SC. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev. 2017 Aug;34:70-81. doi: 10.1016/j.smrv.2016.07.002. Epub 2016 Jul 18. PMID: 27568340.
  11. Iftikhar IH, Kline CE, Youngstedt SD. Effects of exercise training on sleep apnea: a meta-analysis. Lung. 2014 Feb;192(1):175-84. doi: 10.1007/s00408-013-9511-3. PMID: 24077936; PMCID: PMC4216726.
  12. Franklin KA, Lindberg E. Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. J Thorac Dis. 2015 Aug;7(8):1311-22. doi: 10.3978/j.issn.2072-1439.2015.06.11. PMID: 26380759; PMCID: PMC4561280.
  13. Lu LR, Peat JK, Sullivan CE. Snoring in preschool children: prevalence and association with nocturnal cough and asthma. Chest. 2003 Aug;124(2):587-93. doi: 10.1378/chest.124.2.587. PMID: 12907547.
  14. Mukherjee S, Saxena R, Palmer LJ. The genetics of obstructive sleep apnoea. Respirology. 2018 Jan;23(1):18-27. doi: 10.1111/resp.13212. Epub 2017 Nov 7. PMID: 29113020; PMCID: PMC7308164.
  15. Foldvary-Schaefer NR, Waters TE. Sleep-Disordered Breathing. Continuum (Minneap Minn). 2017 Aug;23(4, Sleep Neurology):1093-1116. doi: 10.1212/01.CON.0000522245.13784.f6. PMID: 28777178.
  16. Eskandari D, Zou D, Grote L, Schneider H, Penzel T, Hedner J. Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea. Respir Res. 2017 Jun 28;18(1):130. doi: 10.1186/s12931-017-0607-9. PMID: 28659192; PMCID: PMC5490198.
  17. Reutrakul S, Mokhlesi B. Obstructive Sleep Apnea and Diabetes: A State of the Art Review. Chest. 2017 Nov;152(5):1070-1086. doi: 10.1016/j.chest.2017.05.009. Epub 2017 May 17. PMID: 28527878; PMCID: PMC5812754.
  18. Stanek A, Brożyna-Tkaczyk K, Myśliński W. Oxidative Stress Markers among Obstructive Sleep Apnea Patients. Oxid Med Cell Longev. 2021 Jul 19;2021:9681595. doi: 10.1155/2021/9681595. PMID: 34336121; PMCID: PMC8321764.
  19. Zapater A, Benítez ID, Santamaria-Martos F, Pinilla L, Targa A, De Gonzalo-Calvo D, Torres G, Mínguez O, Cortijo A, Dalmases M, Barbé F, Sánchez-de-la-Torre M. Endogenous controls and microRNA profile in female patients with obstructive sleep apnea. Sci Rep. 2022 Feb 3;12(1):1916. doi: 10.1038/s41598-022-05782-y. PMID: 35115631; PMCID: PMC8813920.
  20. Ozben S, Huseyinoglu N, Hanikoglu F, Guvenc TS, Yildirim BZ, Cort A, Ozdem S, Ozben T. Advanced oxidation protein products and ischaemia-modified albumin in obstructive sleep apnea. Eur J Clin Invest. 2014 Nov;44(11):1045-52. doi: 10.1111/eci.12338. Epub 2014 Oct 4. PMID: 25223839.
  21. Shimony A, Zahger D, Gilutz H, Goldstein H, Orlov G, Merkin M, Shalev A, Ilia R, Douvdevani A. Cell free DNA detected by a novel method in acute ST-elevation myocardial infarction patients. Acute Card Care. 2010 Sep;12(3):109-11. doi: 10.3109/17482941.2010.513732. PMID: 20712451.
  22. Tsai NW, Lin TK, Chen SD, Chang WN, Wang HC, Yang TM, Lin YJ, Jan CR, Huang CR, Liou CW, Lu CH. The value of serial plasma nuclear and mitochondrial DNA levels in patients with acute ischemic stroke. Clin Chim Acta. 2011 Feb 20;412(5-6):476-9. doi: 10.1016/j.cca.2010.11.036. Epub 2010 Dec 3. PMID: 21130757.
  23. Simiakakis M, Kapsimalis F, Chaligiannis E, Loukides S, Sitaras N, Alchanatis M. Lack of effect of sleep apnea on oxidative stress in obstructive sleep apnea syndrome (OSAS) patients. PLoS One. 2012;7(6):e39172. doi: 10.1371/journal.pone.0039172. Epub 2012 Jun 25. PMID: 22761732; PMCID: PMC3382594.
  24. He Y, Chen R, Wang J, Pan W, Sun Y, Han F, Wang Q, Liu C. Neurocognitive impairment is correlated with oxidative stress in patients with moderate-to-severe obstructive sleep apnea hypopnea syndrome. Respir Med. 2016 Nov;120:25-30. doi: 10.1016/j.rmed.2016.09.009. Epub 2016 Sep 9. PMID: 27817812.
  25. Passali D, Corallo G, Petti A, Longini M, Passali FM, Buonocore G, Bellussi LM. A comparative study on oxidative stress role in nasal breathing impairment and obstructive sleep apnoea syndrome. Acta Otorhinolaryngol Ital. 2016 Dec;36(6):490-495. doi: 10.14639/0392-100X-1361. PMID: 28177332; PMCID: PMC5317128.
  26. Borges YG, Cipriano LHC, Aires R, Zovico PVC, Campos FV, de Araújo MTM, Gouvea SA. Oxidative stress and inflammatory profiles in obstructive sleep apnea: are short-term CPAP or aerobic exercise therapies effective? Sleep Breath. 2020 Jun;24(2):541-549. doi: 10.1007/s11325-019-01898-0. Epub 2019 Jul 16. PMID: 31313021.
  27. Bauça JM, Yañez A, Fueyo L, de la Peña M, Pierola J, Sánchez-de-la-Torre A, Mediano O, Cabriada-Nuño V, Masdeu MJ, Teran-Santos J, Duran-Cantolla J, Masa JF, Abad J, Sanchez-de-la-Torre M, Barbé F, Barceló A; Spanish Sleep Network. Cell Death Biomarkers and Obstructive Sleep Apnea: Implications in the Acute Coronary Syndrome. Sleep. 2017 May 1;40(5). doi: 10.1093/sleep/zsx049. PMID: 28419383.
  28. Maniaci A, Iannella G, Cocuzza S, Vicini C, Magliulo G, Ferlito S, Cammaroto G, Meccariello G, De Vito A, Nicolai A, Pace A, Artico M, Taurone S. Oxidative Stress and Inflammation Biomarker Expression in Obstructive Sleep Apnea Patients. J Clin Med. 2021 Jan 13;10(2):277. doi: 10.3390/jcm10020277. PMID: 33451164; PMCID: PMC7828672.
  29. Fernández-Bello I, Monzón Manzano E, García Río F, Justo Sanz R, Cubillos-Zapata C, Casitas R, Sánchez B, Jaureguizar A, Acuña P, Alonso-Fernández A, Álvarez Román MT, Jiménez Yuste V, Butta NV. Procoagulant State of Sleep Apnea Depends on Systemic Inflammation and Endothelial Damage. Arch Bronconeumol. 2022 Feb;58(2):117-124. English, Spanish. doi: 10.1016/j.arbres.2020.11.017. Epub 2020 Dec 24. PMID: 33461785.
  30. Shin C, Kim JK, Kim JH, Jung KH, Cho KJ, Lee CK, Lee SG. Increased cell-free DNA concentrations in patients with obstructive sleep apnea. Psychiatry Clin Neurosci. 2008 Dec;62(6):721-7. doi: 10.1111/j.1440-1819.2008.01876.x. PMID: 19068010.
  31. Kang IG, Jung JH, Kim ST. The effect of obstructive sleep apnea on DNA damage and oxidative stress. Clin Exp Otorhinolaryngol. 2013 Jun;6(2):68-72. doi: 10.3342/ceo.2013.6.2.68. Epub 2013 Jun 14. PMID: 23799162; PMCID: PMC3687064.
  32. Bilal N, Kurutas EB, Orhan I, Bilal B, Doganer A. Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea. Sleep Breath. 2021 Jun;25(2):819-826. doi: 10.1007/s11325-020-02161-7. Epub 2020 Aug 10. Erratum in: Sleep Breath. 2021 Jun;25(2):827. doi: 10.1007/s11325-021-02317-z. PMID: 32776303.
  33. Ye L, Ma GH, Chen L, Li M, Liu JL, Yang K, Li QY, Li N, Wan HY. Quantification of circulating cell-free DNA in the serum of patients with obstructive sleep apnea-hypopnea syndrome. Lung. 2010 Dec;188(6):469-74. doi: 10.1007/s00408-010-9253-4. Epub 2010 Jul 29. PMID: 20668869.
  34. Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. 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 Mar 15;13(3):479-504. doi: 10.5664/jcsm.6506. PMID: 28162150; PMCID: PMC5337595.
  35. Crook S, Sievi NA, Bloch KE, Stradling JR, Frei A, Puhan MA, Kohler M. Minimum important difference of the Epworth Sleepiness Scale in obstructive sleep apnoea: estimation from three randomised controlled trials. Thorax. 2019 Apr;74(4):390-396. doi: 10.1136/thoraxjnl-2018-211959. Epub 2018 Aug 12. PMID: 30100576.
  36. Ermakov AV, Konkova MS, Kostyuk SV, Izevskaya VL, Baranova A, Veiko NN. Oxidized extracellular DNA as a stress signal in human cells. Oxid Med Cell Longev. 2013;2013:649747. doi: 10.1155/2013/649747. Epub 2013 Mar 6. PMID: 23533696; PMCID: PMC3606786.
  37. Zhou L, Chen P, Peng Y, Ouyang R. Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome. Oxid Med Cell Longev. 2016;2016:9626831. doi: 10.1155/2016/9626831. Epub 2016 Sep 28. PMID: 27774119; PMCID: PMC5059616.
  38. Tóthová L, Hodosy J, Mucska I, Celec P. Salivary markers of oxidative stress in patients with obstructive sleep apnea treated with continuous positive airway pressure. Sleep Breath. 2014 Sep;18(3):563-70. doi: 10.1007/s11325-013-0919-z. Epub 2013 Dec 10. PMID: 24323279.
  39. Muñoz-Hernandez R, Vallejo-Vaz AJ, Sanchez Armengol A, Moreno-Luna R, Caballero-Eraso C, Macher HC, Villar J, Merino AM, Castell J, Capote F, Stiefel P. Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP. PLoS One. 2015 Mar 27;10(3):e0122091. doi: 10.1371/journal.pone.0122091. PMID: 25815511; PMCID: PMC4376903.
  40. Kanbay A, Kokturk O, Ciftci TU, Tavil Y, Bukan N. Comparison of serum adiponectin and tumor necrosis factor-alpha levels between patients with and without obstructive sleep apnea syndrome. Respiration. 2008;76(3):324-30. doi: 10.1159/000134010. Epub 2008 May 19. PMID: 18487876.
  41. Imani MM, Sadeghi M, Khazaie H, Emami M, Sadeghi Bahmani D, Brand S. Serum and Plasma Tumor Necrosis Factor Alpha Levels in Individuals with Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Meta-Regression. Life (Basel). 2020 Jun 12;10(6):87. doi: 10.3390/life10060087. PMID: 32545460; PMCID: PMC7345342.
  42. Georgoulis M, Yiannakouris N, Tenta R, Kechribari I, Lamprou K, Vagiakis E, Kontogianni MD. Improvements in Plasma Tumor Necrosis Factor-Alpha Levels after a Weight-Loss Lifestyle Intervention in Patients with Obstructive Sleep Apnea. Life (Basel). 2022 Aug 17;12(8):1252. doi: 10.3390/life12081252. PMID: 36013431; PMCID: PMC9410143.
  43. Archontogeorgis K, Nena E, Papanas N, Steiropoulos P. Biomarkers to improve diagnosis and monitoring of obstructive sleep apnea syndrome: current status and future perspectives. Pulm Med. 2014;2014:930535. doi: 10.1155/2014/930535. Epub 2014 Nov 27. PMID: 25538852; PMCID: PMC4265695.
  44. Sarac F, Basoglu OK, Gunduz C, Bayrak H, Biray Avci C, Akcicek F. Association of osteopontin and tumor necrosis factor-α levels with insulin resistance in obese patients with obstructive sleep apnea syndrome. J Endocrinol Invest. 2011 Jul-Aug;34(7):528-33. doi: 10.3275/7287. Epub 2010 Oct 8. PMID: 20935448.
  45. Cao Y, Song Y, Ning P, Zhang L, Wu S, Quan J, Li Q. Association between tumor necrosis factor alpha and obstructive sleep apnea in adults: a meta-analysis update. BMC Pulm Med. 2020 Aug 12;20(1):215. doi: 10.1186/s12890-020-01253-0. PMID: 32787816; PMCID: PMC7425010.

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Received March 30, 2026.
Accepted April 29, 2026.
© 2026 The Author(s). International Journal of Biomedicine is published by IMRDC.
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