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Published in: BMC Pulmonary Medicine 1/2021

Open Access 01-12-2021 | Chronic Obstructive Lung Disease | Research

The polymorphisms of FGFR2 and MGAT5 affect the susceptibility to COPD in the Chinese people

Authors: Xiaobo Li, Guangyu Zhou, Xiaobo Tian, Fei Chen, Guoyao Li, Yipeng Ding

Published in: BMC Pulmonary Medicine | Issue 1/2021

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Abstract

Background

Chronic obstructive pulmonary disease (COPD) is characterized by incomplete reversible airflow limitation and chronic inflammatory response lesions. This study mainly explored whether FGFR2 and MGAT5 polymorphisms affected the risk of COPD in the Chinese people.

Methods

Five variants in FGFR2 and MGAT5 were chosen and genotyped using Agena MassARRAY platform from 315 COPD patients and 314 healthy controls. The correlation of FGFR2 and MGAT5 with COPD susceptibility was evaluated with odds ratio (OR) and 95% confidence interval (CI) via logistic regression.

Results

We found rs2420915 enhanced the risk of COPD, while rs6430491, rs2593704 reduced the susceptibility of COPD (p < 0.05). Rs2420915 could promote the incidence of COPD in the elderly and nonsmokers. Rs1907240 and rs2257129 also increased the susceptibility to COPD in nonsmokers (p < 0.05). MGAT5-rs2593704 played a protective role in COPD development in different subgroups (age ≤ 70, male, smokers, and individuals with BMI ≤ 24 kg/m2). Meanwhile, rs6430491 was linked with a lower risk of COPD in nonsmoking and BMI ≤ 24 kg/m2 subgroups.

Conclusions

We concluded that FGFR2 and MGAT5 genetic polymorphisms are correlated with the risk of COPD in the Chinese people. These data underscored the important role of FGFR2 and MGAT5 gene in the occurrence of COPD and provided new biomarkers for COPD treatment.
Trial registration: NA.
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Literature
1.
go back to reference Flattet Y, Garin N, Serratrice J, Perrier A, Stirnemann J, Carballo S. Determining prognosis in acute exacerbation of COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:467–75.CrossRef Flattet Y, Garin N, Serratrice J, Perrier A, Stirnemann J, Carballo S. Determining prognosis in acute exacerbation of COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:467–75.CrossRef
2.
go back to reference Donaldson GC, Wilkinson TM, Hurst JR, Perera WR, Wedzicha JA. Exacerbations and time spent outdoors in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;171(5):446–52.CrossRef Donaldson GC, Wilkinson TM, Hurst JR, Perera WR, Wedzicha JA. Exacerbations and time spent outdoors in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;171(5):446–52.CrossRef
3.
go back to reference Salvi S. Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clin Chest Med. 2014;35(1):17–27.CrossRef Salvi S. Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clin Chest Med. 2014;35(1):17–27.CrossRef
4.
go back to reference Eisner MD, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D, et al. An official American Thoracic Society public policy statement: novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182(5):693–718.CrossRef Eisner MD, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D, et al. An official American Thoracic Society public policy statement: novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182(5):693–718.CrossRef
5.
go back to reference Shukla RK, Kant S, Bhattacharya S, Mittal B. Association of genetic polymorphism of GSTT1, GSTM1 and GSTM3 in COPD patients in a north Indian population. COPD. 2011;8(3):167–72.CrossRef Shukla RK, Kant S, Bhattacharya S, Mittal B. Association of genetic polymorphism of GSTT1, GSTM1 and GSTM3 in COPD patients in a north Indian population. COPD. 2011;8(3):167–72.CrossRef
6.
go back to reference Manichaikul A, Hoffman EA, Smolonska J, Gao W, Cho MH, Baumhauer H, et al. Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study. Am J Respir Crit Care Med. 2014;189(4):408–18.CrossRef Manichaikul A, Hoffman EA, Smolonska J, Gao W, Cho MH, Baumhauer H, et al. Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study. Am J Respir Crit Care Med. 2014;189(4):408–18.CrossRef
7.
go back to reference Du Y, Zhang H, Xu Y, Ding Y, Chen X, Mei Z, et al. Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility. Int J Chron Obstruct Pulmon Dis. 2019;14:2081–8.CrossRef Du Y, Zhang H, Xu Y, Ding Y, Chen X, Mei Z, et al. Association among genetic polymorphisms of GSTP1, HO-1, and SOD-3 and chronic obstructive pulmonary disease susceptibility. Int J Chron Obstruct Pulmon Dis. 2019;14:2081–8.CrossRef
8.
go back to reference Wang B, Liang B, Yang J, Xiao J, Ma C, Xu S, et al. Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese. Clin Biochem. 2013;46(16–17):1683–8.CrossRef Wang B, Liang B, Yang J, Xiao J, Ma C, Xu S, et al. Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese. Clin Biochem. 2013;46(16–17):1683–8.CrossRef
9.
go back to reference Yoon HK, Hu HJ, Rhee CK, Shin SH, Oh YM, Lee SD, et al. Polymorphisms in PDE4D are associated with a risk of COPD in non-emphysematous Koreans. COPD. 2014;11(6):652–8.CrossRef Yoon HK, Hu HJ, Rhee CK, Shin SH, Oh YM, Lee SD, et al. Polymorphisms in PDE4D are associated with a risk of COPD in non-emphysematous Koreans. COPD. 2014;11(6):652–8.CrossRef
10.
go back to reference Ding Y, Li Q, Feng Q, Xu D, Wu C, Zhao J, et al. CYP2B6 genetic polymorphisms influence chronic obstructive pulmonary disease susceptibility in the Hainan population. Int J Chron Obstruct Pulmon Dis. 2019;14:2103–15.CrossRef Ding Y, Li Q, Feng Q, Xu D, Wu C, Zhao J, et al. CYP2B6 genetic polymorphisms influence chronic obstructive pulmonary disease susceptibility in the Hainan population. Int J Chron Obstruct Pulmon Dis. 2019;14:2103–15.CrossRef
11.
go back to reference Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235–53.CrossRef Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235–53.CrossRef
12.
go back to reference Theelen WS, Mittempergher L, Willems SM, Bosma AJ, Peters DD, van der Noort V, et al. FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer. J Pathol Clin Res. 2016;2(4):223–33.CrossRef Theelen WS, Mittempergher L, Willems SM, Bosma AJ, Peters DD, van der Noort V, et al. FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non-small cell lung cancer. J Pathol Clin Res. 2016;2(4):223–33.CrossRef
13.
go back to reference Yuan T, Klinkhammer K, Lyu H, Gao S, Yuan J, Hopkins S, et al. Temporospatial expression of Fgfr1 and 2 during lung development, homeostasis, and regeneration. Front Pharmacol. 2020;11:120.CrossRef Yuan T, Klinkhammer K, Lyu H, Gao S, Yuan J, Hopkins S, et al. Temporospatial expression of Fgfr1 and 2 during lung development, homeostasis, and regeneration. Front Pharmacol. 2020;11:120.CrossRef
14.
go back to reference Dorry SJ, Ansbro BO, Ornitz DM, Mutlu GM, Guzy RD. FGFR2 is required for AEC2 homeostasis and survival after bleomycin-induced lung injury. Am J Respir Cell Mol Biol. 2020;62(5):608–21.CrossRef Dorry SJ, Ansbro BO, Ornitz DM, Mutlu GM, Guzy RD. FGFR2 is required for AEC2 homeostasis and survival after bleomycin-induced lung injury. Am J Respir Cell Mol Biol. 2020;62(5):608–21.CrossRef
15.
go back to reference Jieming G, Liu C, Yang Y, Mo S, Yang X, Wang J. Inhibitory effects of msFGFR2c on the epithelial-to-mesenchymal transition of AE2 cells in pulmonary fibrosis. Biotech Lett. 2020;42(6):1061–70.CrossRef Jieming G, Liu C, Yang Y, Mo S, Yang X, Wang J. Inhibitory effects of msFGFR2c on the epithelial-to-mesenchymal transition of AE2 cells in pulmonary fibrosis. Biotech Lett. 2020;42(6):1061–70.CrossRef
16.
go back to reference Nabi IR, Shankar J, Dennis JW. The galectin lattice at a glance. J Cell Sci. 2015;128(13):2213–9.CrossRef Nabi IR, Shankar J, Dennis JW. The galectin lattice at a glance. J Cell Sci. 2015;128(13):2213–9.CrossRef
17.
go back to reference Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, et al. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell. 2007;129(1):123–34.CrossRef Lau KS, Partridge EA, Grigorian A, Silvescu CI, Reinhold VN, Demetriou M, et al. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell. 2007;129(1):123–34.CrossRef
18.
go back to reference Zhou X, Chen H, Wang Q, Zhang L, Zhao J. Knockdown of Mgat5 inhibits CD133+ human pulmonary adenocarcinoma cell growth in vitro and in vivo. Clin Invest Med. 2011;34(3):E155–62.CrossRef Zhou X, Chen H, Wang Q, Zhang L, Zhao J. Knockdown of Mgat5 inhibits CD133+ human pulmonary adenocarcinoma cell growth in vitro and in vivo. Clin Invest Med. 2011;34(3):E155–62.CrossRef
19.
go back to reference Cai J, Huang J, Wang W, Zeng J, Wang P. miR-124-3p regulates FGF2-EGFR pathway to overcome pemetrexed resistance in lung adenocarcinoma cells by targeting MGAT5. Cancer Manag Res. 2020;12:11597–609.CrossRef Cai J, Huang J, Wang W, Zeng J, Wang P. miR-124-3p regulates FGF2-EGFR pathway to overcome pemetrexed resistance in lung adenocarcinoma cells by targeting MGAT5. Cancer Manag Res. 2020;12:11597–609.CrossRef
20.
go back to reference Elek Z, Kovács Z, Keszler G, Szabó M, Csanky E, Luo J, et al. High throughput multiplex SNP-analysis in chronic obstructive pulmonary disease and lung cancer. Curr Mol Med. 2020;20(3):185–93.CrossRef Elek Z, Kovács Z, Keszler G, Szabó M, Csanky E, Luo J, et al. High throughput multiplex SNP-analysis in chronic obstructive pulmonary disease and lung cancer. Curr Mol Med. 2020;20(3):185–93.CrossRef
21.
go back to reference Du J, Jin T, Cao Y, Chen J, Guo Y, Sun M, et al. Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China. Medicine. 2016;95(37):e4794.CrossRef Du J, Jin T, Cao Y, Chen J, Guo Y, Sun M, et al. Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China. Medicine. 2016;95(37):e4794.CrossRef
22.
go back to reference Zhao Q, Liao S, Wei H, Liu D, Li J, Zhang X, et al. CDKN2BAS polymorphisms are associated with coronary heart disease risk a Han Chinese population. Oncotarget. 2016;7(50):82046–54.CrossRef Zhao Q, Liao S, Wei H, Liu D, Li J, Zhang X, et al. CDKN2BAS polymorphisms are associated with coronary heart disease risk a Han Chinese population. Oncotarget. 2016;7(50):82046–54.CrossRef
23.
go back to reference Katoh M. Cancer genomics and genetics of FGFR2 (Review). Int J Oncol. 2008;33(2):233–7.PubMed Katoh M. Cancer genomics and genetics of FGFR2 (Review). Int J Oncol. 2008;33(2):233–7.PubMed
24.
go back to reference Yu ZH, Wang DD, Zhou ZY, He SL, Chen AA, Wang J. Mutant soluble ectodomain of fibroblast growth factor receptor-2 IIIc attenuates bleomycin-induced pulmonary fibrosis in mice. Biol Pharm Bull. 2012;35(5):731–6.CrossRef Yu ZH, Wang DD, Zhou ZY, He SL, Chen AA, Wang J. Mutant soluble ectodomain of fibroblast growth factor receptor-2 IIIc attenuates bleomycin-induced pulmonary fibrosis in mice. Biol Pharm Bull. 2012;35(5):731–6.CrossRef
25.
go back to reference Masunaga A, Nagashio R, Iwamoto S, Takeyama N, Sato Y, Miyazaki A, et al. A case of pulmonary papillary adenoma: possible relationship between tumor histogenesis/tumorigenesis and fibroblast growth factor receptor 2 IIIb. Pathol Int. 2012;62(9):640–5.CrossRef Masunaga A, Nagashio R, Iwamoto S, Takeyama N, Sato Y, Miyazaki A, et al. A case of pulmonary papillary adenoma: possible relationship between tumor histogenesis/tumorigenesis and fibroblast growth factor receptor 2 IIIb. Pathol Int. 2012;62(9):640–5.CrossRef
26.
go back to reference Yuan T, Volckaert T, Redente EF, Hopkins S, Klinkhammer K, Wasnick R, et al. FGF10-FGFR2B signaling generates basal cells and drives alveolar epithelial regeneration by bronchial epithelial stem cells after lung injury. Stem Cell Rep. 2019;12(5):1041–55.CrossRef Yuan T, Volckaert T, Redente EF, Hopkins S, Klinkhammer K, Wasnick R, et al. FGF10-FGFR2B signaling generates basal cells and drives alveolar epithelial regeneration by bronchial epithelial stem cells after lung injury. Stem Cell Rep. 2019;12(5):1041–55.CrossRef
27.
go back to reference Li B, Su S, Zhang MY, He L, Wang QD, He K. Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line. Mol Med Rep. 2016;13(1):469–76.CrossRef Li B, Su S, Zhang MY, He L, Wang QD, He K. Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line. Mol Med Rep. 2016;13(1):469–76.CrossRef
28.
go back to reference Hassani Z, Saleh A, Turpault S, Khiati S, Morelle W, Vignon J, et al. Phostine PST3.1a targets MGAT5 and inhibits glioblastoma-initiating cell invasiveness and proliferation. Mol Cancer Res MCR. 2017;15(10):1376–87.CrossRef Hassani Z, Saleh A, Turpault S, Khiati S, Morelle W, Vignon J, et al. Phostine PST3.1a targets MGAT5 and inhibits glioblastoma-initiating cell invasiveness and proliferation. Mol Cancer Res MCR. 2017;15(10):1376–87.CrossRef
29.
go back to reference Dosaka-Akita H, Miyoshi E, Suzuki O, Itoh T, Katoh H, Taniguchi N. Expression of N-acetylglucosaminyltransferase v is associated with prognosis and histology in non-small cell lung cancers. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(5):1773–9.CrossRef Dosaka-Akita H, Miyoshi E, Suzuki O, Itoh T, Katoh H, Taniguchi N. Expression of N-acetylglucosaminyltransferase v is associated with prognosis and histology in non-small cell lung cancers. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(5):1773–9.CrossRef
30.
go back to reference Zhao H, Yang W, Qiu R, Li J, Xin Q, Wang X, et al. An intronic variant associated with systemic lupus erythematosus changes the binding affinity of Yinyang1 to downregulate WDFY4. Genes Immun. 2012;13(7):536–42.CrossRef Zhao H, Yang W, Qiu R, Li J, Xin Q, Wang X, et al. An intronic variant associated with systemic lupus erythematosus changes the binding affinity of Yinyang1 to downregulate WDFY4. Genes Immun. 2012;13(7):536–42.CrossRef
31.
go back to reference Seo S, Takayama K, Uno K, Ohi K, Hashimoto R, Nishizawa D, et al. Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene. PLoS ONE. 2013;8(10):e76960.CrossRef Seo S, Takayama K, Uno K, Ohi K, Hashimoto R, Nishizawa D, et al. Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene. PLoS ONE. 2013;8(10):e76960.CrossRef
Metadata
Title
The polymorphisms of FGFR2 and MGAT5 affect the susceptibility to COPD in the Chinese people
Authors
Xiaobo Li
Guangyu Zhou
Xiaobo Tian
Fei Chen
Guoyao Li
Yipeng Ding
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2021
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-021-01498-3

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