MMP-9 genetic polymorphism may confer susceptibility to COPD

Jiang, Shengli; Yang, Ziyu; Yy, Chen; He, Zhiwei; Zhou, Yajuan; Gao, Yan; Q, Zhang; Mq, Tan

doi:10.4238/gmr.15026272

Cited by 18 publications

(18 citation statements)

References 31 publications

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“…Recent genome-wide association studies have also identified genetic predisposition, in particular alpha-1 antitrypsin deficiency, as an important factor in the development of COPD (Ding et al, 2015;Jiang et al, 2016;Siedlinski et al, 2013). There is clear heterogeneity in the clinical manifestations of COPD, which are greatly attributed to these environmental and genetic cues.…”

Section: Causes and Pathophysiology Of Copdmentioning

confidence: 99%

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

Chan

Selemidis

Bozinovski

et al. 2019

Pharmacology & Therapeutics

116

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a b s t r a c t a r t i c l e i n f oChronic obstructive pulmonary disease (COPD) is a major incurable global health burden and is currently the 4th largest cause of death in the world. Importantly, much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities (e.g. skeletal muscle wasting, ischemic heart disease, cognitive dysfunction) and infective viral and bacterial acute exacerbations (AECOPD). Current pharmacological treatments for COPD are relatively ineffective and the development of effective therapies has been severely hampered by the lack of understanding of the mechanisms and mediators underlying COPD. Since comorbidities have a tremendous impact on the prognosis and severity of COPD, the 2015 American Thoracic Society/European Respiratory Society (ATS/ERS) Research Statement on COPD urgently called for studies to elucidate the pathobiological mechanisms linking COPD to its comorbidities. It is now emerging that up to 50% of COPD patients have metabolic syndrome (MetS) as a comorbidity. It is currently not clear whether metabolic syndrome is an independent co-existing condition or a direct consequence of the progressive lung pathology in COPD patients. As MetS has important clinical implications on COPD outcomes, identification of disease mechanisms linking COPD to MetS is the key to effective therapy. In this comprehensive review, we discuss the potential mechanisms linking MetS to COPD and hence plausible therapeutic strategies to treat this debilitating comorbidity of COPD.

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Section: Causes and Pathophysiology Of Copdmentioning

confidence: 99%

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

Chan

Selemidis

Bozinovski

et al. 2019

Pharmacology & Therapeutics

116

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“…MMP genetic polymorphisms and levels of gene expression have been associated with several diseases, including chronic obstructive pulmonary disease, coronary heart disease, rheumatoid arthritis, and systemic lupus erythematosus (Schirmer et al, 2009;Scherer et al, 2010;Bahrehmand et al, 2015;Jiang et al, 2016;Ma et al, 2015Ma et al, , 2016. Different studies have addressed the MMP serum levels and MMP gene expression in SSc (Young-Min et al, 2001;Kikuchi et al, 2002;Toubi et al, 2002;Meng et al, 2008;Brown et al, 2012;Frost et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

et al. 2016

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ABSTRACT. The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T 2 T.F. Rech et al. Genetics and Molecular Research 15 (4): gmr15049077(rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features.

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“…But a meta-analysis showed that MMP9 rs3918242 C > T significantly correlated with increased susceptibility to COPD. 18 In clinical manifestations, 37.5% of patients with atopic COPD had at least one exacerbation of the disease, while only 27.5% of patients with non-atopic COPD had at least one exacerbation of the disease. This may be due to the fact that patients with atopic COPD are more susceptible to the influence of allergens in the air, which can cause acute exacerbation due to the stimulation of allergens.…”

Section: Discussionmentioning

confidence: 95%

<p>Increased MMP8 Levels in Atopic Chronic Obstructive Pulmonary Disease: A Study Testing Multiple Immune Factors in Atopic and Non-Atopic Patients</p>

Cai

Xue

et al. 2020

COPD

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The aim of this study was to analyse the level of serum matrix metalloproteinases (MMPs) in atopic and non-atopic COPD patients, providing guidance for clinical practice and theory for atopic COPD. Methods: Blood samples from 50 adult male patients with COPD, including 17 atopic and 33 non-atopic patients, were submitted for detection of MMP8, MMP9, surfactant associated protein D (SPD), noradrenaline (NE), leukotriene (LT) B4, recombinant proteoglycan (PRG4), Phadiatop sIgE, and tIgE levels. Patients' Modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), pulmonary function test results, FeNO, blood cell ratio and induced sputum were collected. Results: The level of serum tIgE in patients with atopic COPD [1876.00 kU/l (760.50, 5347.00)] was significantly higher than in patients with non-atopic COPD [377.00 kU/l (93.50, 581.50), P < 0.001]. The MMP8 levels in atopic COPD (1600 ± 1181 ng/mL) were significantly higher than in non-atopic COPD (973.3 ±921.5 ng/mL, P = 0.0494), but there was no significant difference in MMP9, SPD, NE, LTB4, and PRG4 levels between the two groups. In atopic COPD patients, the rate of leukocyte (r s = 0.63, P < 0.001) and neutrophil (r s = 0.54, P < 0.05) were positively correlated with MMP8 levels, while lymphocyte rate was negatively correlated with MMP8 (r s = −0.70, P < 0.001) and MMP9 levels (r s = −0.54, P < 0.05). Optimal scale analysis showed that NE was most closely related to the basophil rate from induced sputum and FeNO levels (Cronbach's alpha = 85.1%). Interestingly, all atopic COPD patients with mMRC ≥2, CAT ≥ 10, and CCQ ≥16 exhibited MMP8 levels >1000 ng/mL. Conclusion: In general, tIgE and MMP8 levels were higher in atopic COPD patients than in non-atopic patients. NE levels were closely correlated with the basophil rate of induced sputum and FeNO levels, which may play an important role in the pathogenesis and development of atopic COPD.

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MMP-9 genetic polymorphism may confer susceptibility to COPD

Cited by 18 publications

References 31 publications

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

<p>Increased MMP8 Levels in Atopic Chronic Obstructive Pulmonary Disease: A Study Testing Multiple Immune Factors in Atopic and Non-Atopic Patients</p>

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