Tumor necrosis factor‑&alpha; ‑308 G/A genetic polymorphism in patients with chronic obstructive pulmonary disease presenting with hyperactive airways

Hipolito,Pia Monique D.; Quilala,Peter F.; Dimamay,Mark Pierre S.; Liles,Veni R.; Yungca,Mica Xiena; Baclig,Michael O.

doi:10.3892/br.2024.1802

Tumor necrosis factor‑α ‑308 G/A genetic polymorphism in patients with chronic obstructive pulmonary disease presenting with hyperactive airways

Authors:
- Pia Monique D. Hipolito
- Peter F. Quilala
- Mark Pierre S. Dimamay
- Veni R. Liles
- Mica Xiena Yungca
- Michael O. Baclig
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Affiliations: Department of Emergency Medicine, St. Luke's Medical Center, Quezon City 1112, Philippines, Center for Basic Science Research, St. Luke's Medical Center, Quezon City 1112, Philippines, Department of Molecular Medicine, St. Luke's Medical Center College of Medicine‑William H. Quasha Memorial, Quezon City 1112, Philippines
Published online on: June 12, 2024 https://doi.org/10.3892/br.2024.1802
Article Number: 113

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Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. COPD is often diagnosed late in the disease leading to a delay in management. Notably, tumor necrosis factor‑α (TNF‑α) polymorphisms may serve an important role in the development of COPD. A single‑center, case‑control study was conducted to determine the presence of the TNF‑α ‑308 G/A polymorphism among patients diagnosed with COPD presenting with hyperactive airways, patients without COPD presenting with hyperactive airways, and normal study participants without pulmonary comorbidities. Three genotypes: G/G (94%; 157/167), G/A (5%; 9/167) and A/A (1%; 1/167) were detected by quantitative PCR. The present study showed that the presence of the TNF‑α ‑308 G/A polymorphism reduced the odds of having hyperactive airways with COPD by 29.3% and hyperactive airways without COPD by 26.3%. Multinomial logistic regression analysis showed that having the TNF‑α ‑308 G/A polymorphism did not significantly reduce the odds of having hyperactive airways with COPD and without COPD compared to those with the G/G genotype. In conclusion, the presence of the TNF‑α ‑308 G/A gene polymorphism showed no significant association with patients with COPD with or without hyperactive airways. The presence of the TNF‑α ‑308 G/A polymorphism instead had a weak association with the reduction in the development of COPD regardless of the presence or absence of airway hyperactivity.

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1	Global Initiative for Chronic Obstructive Lung Disease (GOLD): Pocket Guide to COPD Diagnosis, Management, and Prevention. GOLD, 2020.
2	American Academy of Family Physicians: COPD and Asthma: Differential Diagnosis. American Academy of Family Physicians, 2016.
3	Clinical Practice Guidelines in the Practice and Management of Chronic Obstructive Pulmonary Disease (COPD) in the Philippines. Council on COPD and Pulmonary Rehabilitation Philippine College of Physicians, 2009.
4	Ramadan F: New trends in asthma. J Med Liban. 41:27–31. 1993.PubMed/NCBI
5	Martinez CH, Mannino DM, Jaimes FA, Curtis JL, Han MK, Hansel NN and Diaz AA: Undiagnosed obstructive lung disease in the United States. Associated factors and long-term mortality. Ann Am Thorac Soc. 12:1788–1795. 2015.PubMed/NCBI View Article : Google Scholar
6	Global Initiative for Chronic Obstructive Lung Disease (GOLD): Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD, and Asthma-COPD Overlap Syndrome (ACOS). GOLD, 2015.
7	Malaviya R, Laskin JD and Laskin DL: Anti-TNFα therapy in inflammatory lung diseases. Pharmacol Ther. 180:90–98. 2017.PubMed/NCBI View Article : Google Scholar
8	Chung KF: Inflammatory mediators in chronic obstructive pulmonary disease. Curr Drug Targets Inflamm Allergy. 4:619–625. 2005.PubMed/NCBI View Article : Google Scholar
9	Khair OA, Devalia JL, Abdelaziz MM, Sapsford RJ, Tarraf H and Davies RJ: Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6, IL-8, TNF-alpha, and expression of ICAM-1 in cultured human bronchial epithelial cells. Eur Respir J. 7:2109–2116. 1994.PubMed/NCBI View Article : Google Scholar
10	Wedzicha JA, Seemungal TA, MacCallum PK, Paul EA, Donaldson GC, Bhowmik A, Jeffries DJ and Meade TW: Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost. 84:210–215. 2000.PubMed/NCBI
11	Lin YJ, Chen RH, Wan L, Sheu JC, Huang CM, Lin CW, Chen SY, Lai CH, Lan YC, Hsueh KC, et al: Association of TNF-alpha gene polymorphisms with systemic lupus erythematosus in Taiwanese patients. Lupus. 18:974–979. 2009.PubMed/NCBI View Article : Google Scholar
12	Mosaad YM, Abdelsalam A and El-Bassiony SR: Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. Int J Immunogenet. 38:427–433. 2011.PubMed/NCBI View Article : Google Scholar
13	Xia Z, Wang Y, Liu F, Shu H and Huang P: Association between TNF-α-308, +489, -238 polymorphism, and COPD susceptibility: An updated meta-analysis and trial sequential analysis. Front Genet. 12(772032)2022.PubMed/NCBI View Article : Google Scholar
14	Yu S, Xue M, Yan Z, Song B, Hong H and Gao X: Correlation between TNF-α -308 and +489 gene polymorphism and acute exacerbation of chronic obstructive pulmonary diseases. Biomed Res Int. 2021(6661281)2021.PubMed/NCBI View Article : Google Scholar
15	Zhang L, Gu H, Gu Y and Zeng X: Association between TNF-α -308 G/A polymorphism and COPD susceptibility: A meta-analysis update. Int J Chron Obstruct Pulmon Dis. 11:1367–1379. 2016.PubMed/NCBI View Article : Google Scholar
16	Sakao S, Tatsumi K, Igari H, Shino Y, Shirasawa H and Kuriyama T: Association of tumor necrosis factor alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 163:420–422. 2001.PubMed/NCBI View Article : Google Scholar
17	Huang SL, Su CH and Chang SC: Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med. 156:1436–1439. 1997.PubMed/NCBI View Article : Google Scholar
18	Saba N, Yusuf O, Rehman S, Munir S, Bashir N, Mansoor A and Raja Kaukab G: Association of tumor necrosis factor alpha 308 G/A polymorphism with asthma in Pakistani population. Iran J Allergy Asthma Immunol. 14:287–291. 2015.PubMed/NCBI
19	Mukhopadhyay S, Hoidal JR and Mukherjee TK: Role of TNF-alpha in pulmonary pathophysiology. Respir Res. 7(125)2006.PubMed/NCBI View Article : Google Scholar
20	Matera MG, Calzetta L and Cazzola M: TNF-alpha inhibitors in asthma and COPD: We must not throw the baby out with the bath water. Pulm Pharmacol Ther. 23:121–128. 2010.PubMed/NCBI View Article : Google Scholar
21	Rodriguez S, Gaunt TR and Day IN: Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 169:505–514. 2009.PubMed/NCBI View Article : Google Scholar
22	Santana G, Bendicho MT, Santana TC, Reis LB, Lemaire D and Lyra AC: The TNF-α -308 polymorphism may affect the severity of Crohn's disease. Clinics (Sao Paulo). 66:1373–1378. 2011.PubMed/NCBI View Article : Google Scholar
23	Wilson AG, Symons JA, McDowell TL, McDevitt HO and Duff GW: Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 94:3195–3199. 1997.PubMed/NCBI View Article : Google Scholar
24	Sakao S, Tatsumi K, Igari H, Watanabe R, Shino Y, Shirasawa H and Kuriyama T: Association of tumor necrosis factor-alpha gene promoter polymorphism with low attenuation areas on high-resolution CT in patients with COPD. Chest. 122:416–420. 2002.PubMed/NCBI View Article : Google Scholar
25	Gingo MR, Silveira LJ, Miller YE, Friedlander AL, Cosgrove GP, Chan ED, Maier LA and Bowler RP: Tumour necrosis factor gene polymorphisms are associated with COPD. Eur Respir J. 31:1005–1012. 2008.PubMed/NCBI View Article : Google Scholar
26	Liu C, Ran R, Li X, Liu G, Xie X and Li J: Genetic variants associated with chronic obstructive pulmonary disease risk: Cumulative epidemiological evidence from meta-analyses and genome-wide association studies. Can Respir J. 2022(3982335)2022.PubMed/NCBI View Article : Google Scholar
27	Salimi Asl M, Ahmadi A, Salimian J, Shohani S, Azimzadeh Jamalkandi S and Ghanei M: TNF-α -308 G/A variant and susceptibility to chronic obstructive pulmonary disease: A systematic review and meta-analysis. Cytokine. 123(154763)2019.PubMed/NCBI View Article : Google Scholar