Association of tumor necrosis factor-α gene polymorphism with susceptibility to chronic obstructive pulmonary disease in eastern Heilongjiang Province_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XIE Xiaoran ¹ ^△ ,  BAO Wenhua ¹ ,  YANG Ze ²

1. The Department of Respiratory Medicine, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P. R. China;
2. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, P. R. China;

Corresponding?author：

BAO Wenhua, Email: baowenhua3@sina.com; YANG Ze, Email: yang_ze@sina.com

Keywords：

Tumor necrosis factor α; Gene polymorphism; Chronic obstructive pulmonary disease; High resolution melting curve genotyping; SHEsis genetic imbalance haplotype analysis

DOI：

10.7507/1671-6205.201711001

Video：

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Objective To investigate the association between tumor necrosis factor (TNF)-α gene polymorphism and susceptibility to chronic obstructive pulmonary disease (COPD) in eastern Heilongjiang province.Methods A total of 347 COPD patients in the Department of Respiratory Medicine, the First Affiliated Hospital of Jiamusi University, were enrolled from January 2016 to January 2017. In the same period, 338 healthy subjects in the hospital physical examination center were selected as controls. The genotype of the two groups was analyzed by high resolution melting (HRM) and gene sequencing. The genotype and allele probability of the two groups were compared and analyzed by the SHEsis genetic imbalance haplotype analysis.Results Both TNF-a –308 G/A co-dominant model and recessive model have significant differences between COPD patients and healthy subjects (P=0.036, OR 1.512, 95%CI 1.023 – 2.234; P=0.027, OR 1.202, 95%CI 1.024 – 1.741). –850G/A co-dominant model (P=0.000, OR 1.781, 95%CI 1.363 – 2.329), dominant model (P=0.000, OR 0.391 7, 95%CI 1.363 – 2.329) and hyper-dominant model (P=0.000, OR 2.680, 95%CI 1.728 – 4.156) in the two groups were statistically different. The haploid analysis and haploid genotype analysis showed statistically significant differences (all P<0.05, OR>1, 95%CI>1) at +489, –308, –850 sites by allele A, G, A, respectively between the two groups. There was a significant difference in the lung function between the –308G/A, –863C/A mutant genome and the wild type (P=0.038, P=0.02) in COPD patients according to the classification of lung function.Conclusions A allele in TNF-α –308 and G allele in TNF-α –850 locus may be risk factors for COPD in the eastern Heilongjiang Province, and the risk of homozygous genotype is higher. +489A, –308G and –850A respectively may be the predisposing factor of COPD while the three genotypes of AGA patients were at higher risk. TNF-α –308 A allele and –863 A allele are related to lung function deterioration, and the two sites with A allele in patients with COPD indicate poor lung function.

Citation： XIE Xiaoran, BAO Wenhua, YANG Ze. Association of tumor necrosis factor-α gene polymorphism with susceptibility to chronic obstructive pulmonary disease in eastern Heilongjiang Province. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(3): 217-223. doi: 10.7507/1671-6205.201711001 Copy

1.	中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南. 中華結核和呼吸雜志, 2007, 30(1): 8-17.
2.	Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2017. Available at: http://www.goldcopd.org/. Accessed June 5, 2017.
3.	Zhang S, Wang C, Xi B, et al. Association between the tumour necrosis factor-alpha-308G/A polymorphism and chronic obstructive pulmonary disease: an update. Respirology, 2011, 16(1): 107-115.
4.	Lamprecht B, McBurnie MA, Vollmer WM, et al. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest, 2011, 139(4): 752-763.
5.	Marciniak SJ, Lomas DA. What can naturally occurring mutations tell us about the pathogenesis of COPD?. Thorax, 2009, 64(4): 359-364.
6.	Wei L, Xu D, Qian Y, et al. Comprehensive analysis of gene expression profile in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1103-1109.
7.	Hobbs BD, Hersh CP. Integrative genomics of chronic obstructive pulmonary disease. Biochem Biophys Res Commun, 2014, 452(2): 276-286.
8.	Lee PN, Fry JS. Systematic review of the evidence relating FEV1 decline to giving up smoking. BMC Med, 2010, 8: 84.
9.	Klimentidis YC, Vazquez AI, de Los Campos G, et al. Heritability of pulmonary function estimated from pedigree and whole-genome markers. Front Genet, 2013, 4: 174.
10.	Henderson J, Harrison C. Management of COPD in general practice. Aust Fam Physician C, 2012, 41(11): 841.
11.	Wouters EF, Reynaert NL, Dentener MA, et al. Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection?. Proc Am Thorac Soc, 2009, 6(8): 638-647.
12.	Ji J, von Scheele I, Bergstrom J, et al. Compartment differences of inflammatory activity in chronic obstructive pulmonary disease. Respir Res, 2014, 15: 104.
13.	Keatings VM, Collins PD, Scott DM, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med, 1996, 153(2): 530-534.
14.	Takabatake N, Arao T, Sata M, et al. Circulating levels of soluble Fas ligand in cachexic patients with COPD are higher than those in non-cachexic patients with COPD. Intern Med, 2005, 44(11): 1137-1143.
15.	Eurlings IM, Dentener MA, Mercken EM, et al. A comparative study of matrix remodeling in chronic models for COPD; mechanistic insights into the role of TNF-α. Am J Physiol Lung Cell Mol Physiol, 2014, 307(7): L557-L565.
16.	Zhang L, Gu H, Gu Y, et al. Association between TNF-α -308 G/A polymorphism and COPD susceptibility: a meta-analysis update. Int J Chron Obstruct Pulmon Dis, 2016, 11: 1367-1179.
17.	Cui K, Ge XY, Ma HL. Association of the TNF-α +489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis. Genet Mol Res, 2015, 14(2): 5210-5220.
18.	Cui K, Ge XY, Ma HL. Association of -238G/A and -863C/A polymorphisms in the TNF-α gene with chronic obstructive pulmonary disease based on a meta-analysis. Genet Mol Res, 2013, 12(4): 4981-4989.
19.	中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南(2013 年修訂版). 中華結核和呼吸雜志, 2013, 36(1): 1-10.
20.	慢性阻塞性肺疾病急性加重(AECOPD)診治專家組. 慢性阻塞性肺疾病急性加重(AECOPD)診治中國專家共識(草案). 中華哮喘雜志電子版, 2013, 7(1): 1-13.
21.	Sakao S, Tatusumi K, Igari H, et al. Association of tumor necrosis factor-alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001, 163(2): 420-422.
22.	Huang SL, Su CH, Chang SC, et al. Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(5): 1436-1439.
23.	Ozdogan N, Tutar N, Demir R, et al. Is TNF-α gene polymorphism related to pulmonary functions and prognosis as determined by FEV1, BMI, COPD exacerbation and hospitalization in patients with smoking-related COPD in a Turkish population?. Rev Port Pneumol, 2014, 20(6): 305-310.
24.	Teramoto S, Ishii T, Ishii M, et al. Variation in the tumour necrosis factor-alpha gene is not associated with susceptibility to Asian COPD. Eur Respir J, 2008, 31(3): 682-683.
25.	Gingo MR, Silveira LJ, Miller YE, et al. Tumour necrosis factor gene polymorphisms are associated with COPD. Eur Respir J, 2008, 31(5): 1005-1012.
26.	Chiang CH, Chuang CH, Liu SL, et al. Transforming growth factor-β1 and tumor necrosis factor-α are associated with clinical severity and airflow limitation of COPD in an additive manner. Lung, 2014, 192(1): 95-102.
27.	Kü?ükaycan M, Van Krugten M, Pennings HJ, et al. Tumor necrosis factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease. Respir Res, 2002, 3: 29.

1. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南. 中華結核和呼吸雜志, 2007, 30(1): 8-17.
2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD); 2017. Available at: http://www.goldcopd.org/. Accessed June 5, 2017.
3. Zhang S, Wang C, Xi B, et al. Association between the tumour necrosis factor-alpha-308G/A polymorphism and chronic obstructive pulmonary disease: an update. Respirology, 2011, 16(1): 107-115.
4. Lamprecht B, McBurnie MA, Vollmer WM, et al. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest, 2011, 139(4): 752-763.
5. Marciniak SJ, Lomas DA. What can naturally occurring mutations tell us about the pathogenesis of COPD?. Thorax, 2009, 64(4): 359-364.
6. Wei L, Xu D, Qian Y, et al. Comprehensive analysis of gene expression profile in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1103-1109.
7. Hobbs BD, Hersh CP. Integrative genomics of chronic obstructive pulmonary disease. Biochem Biophys Res Commun, 2014, 452(2): 276-286.
8. Lee PN, Fry JS. Systematic review of the evidence relating FEV1 decline to giving up smoking. BMC Med, 2010, 8: 84.
9. Klimentidis YC, Vazquez AI, de Los Campos G, et al. Heritability of pulmonary function estimated from pedigree and whole-genome markers. Front Genet, 2013, 4: 174.
10. Henderson J, Harrison C. Management of COPD in general practice. Aust Fam Physician C, 2012, 41(11): 841.
11. Wouters EF, Reynaert NL, Dentener MA, et al. Systemic and local inflammation in asthma and chronic obstructive pulmonary disease: is there a connection?. Proc Am Thorac Soc, 2009, 6(8): 638-647.
12. Ji J, von Scheele I, Bergstrom J, et al. Compartment differences of inflammatory activity in chronic obstructive pulmonary disease. Respir Res, 2014, 15: 104.
13. Keatings VM, Collins PD, Scott DM, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med, 1996, 153(2): 530-534.
14. Takabatake N, Arao T, Sata M, et al. Circulating levels of soluble Fas ligand in cachexic patients with COPD are higher than those in non-cachexic patients with COPD. Intern Med, 2005, 44(11): 1137-1143.
15. Eurlings IM, Dentener MA, Mercken EM, et al. A comparative study of matrix remodeling in chronic models for COPD; mechanistic insights into the role of TNF-α. Am J Physiol Lung Cell Mol Physiol, 2014, 307(7): L557-L565.
16. Zhang L, Gu H, Gu Y, et al. Association between TNF-α -308 G/A polymorphism and COPD susceptibility: a meta-analysis update. Int J Chron Obstruct Pulmon Dis, 2016, 11: 1367-1179.
17. Cui K, Ge XY, Ma HL. Association of the TNF-α +489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis. Genet Mol Res, 2015, 14(2): 5210-5220.
18. Cui K, Ge XY, Ma HL. Association of -238G/A and -863C/A polymorphisms in the TNF-α gene with chronic obstructive pulmonary disease based on a meta-analysis. Genet Mol Res, 2013, 12(4): 4981-4989.
19. 中華醫學會呼吸病學分會慢性阻塞性肺疾病學組. 慢性阻塞性肺疾病診治指南(2013 年修訂版). 中華結核和呼吸雜志, 2013, 36(1): 1-10.
20. 慢性阻塞性肺疾病急性加重(AECOPD)診治專家組. 慢性阻塞性肺疾病急性加重(AECOPD)診治中國專家共識(草案). 中華哮喘雜志電子版, 2013, 7(1): 1-13.
21. Sakao S, Tatusumi K, Igari H, et al. Association of tumor necrosis factor-alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001, 163(2): 420-422.
22. Huang SL, Su CH, Chang SC, et al. Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med, 1997, 156(5): 1436-1439.
23. Ozdogan N, Tutar N, Demir R, et al. Is TNF-α gene polymorphism related to pulmonary functions and prognosis as determined by FEV1, BMI, COPD exacerbation and hospitalization in patients with smoking-related COPD in a Turkish population?. Rev Port Pneumol, 2014, 20(6): 305-310.
24. Teramoto S, Ishii T, Ishii M, et al. Variation in the tumour necrosis factor-alpha gene is not associated with susceptibility to Asian COPD. Eur Respir J, 2008, 31(3): 682-683.
25. Gingo MR, Silveira LJ, Miller YE, et al. Tumour necrosis factor gene polymorphisms are associated with COPD. Eur Respir J, 2008, 31(5): 1005-1012.
26. Chiang CH, Chuang CH, Liu SL, et al. Transforming growth factor-β1 and tumor necrosis factor-α are associated with clinical severity and airflow limitation of COPD in an additive manner. Lung, 2014, 192(1): 95-102.
27. Kü?ükaycan M, Van Krugten M, Pennings HJ, et al. Tumor necrosis factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease. Respir Res, 2002, 3: 29.

Chinese Journal of Respiratory and Critical Care Medicine

Association of tumor necrosis factor-α gene polymorphism with susceptibility to chronic obstructive pulmonary disease in eastern Heilongjiang Province

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