Polymorphisms in the promoter region of neutrophil elastase gene and lung cancer risk

Park, Jong Y.; Chen, Lan; Lee, Ji‐Hyun; Sellers, Thomas A.; Tockman, Melvyn S.

doi:10.1016/j.lungcan.2004.11.022

Cited by 15 publications

(8 citation statements)

References 20 publications

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“…This data are in concordance with data from the studies by Taniguchi et al and Park et al [14,15]. When our LC patients were categorized based on the predicted activity of NE, there were significantly more patients with intermediate and high NE activity, compared to those with low activity (91% vs. 9%, respectively).…”

Section: Discussionsupporting

confidence: 92%

“…Luciferase activity assays showed that ELA2 promoter constructs with −903T/−741G genotype had higher activity compared with the −903G/−741A construct. Based on this results, predicted activity of ELA2 genotypes are classified as: low ELA2 activity genotype (−903TG), intermediate ELA2 activity genotypes (−903TT/−741AG and −903TT/ −741AA) and high ELA2 activity genotypes (−903TT/ −741GG) [15].…”

Section: Introductionmentioning

confidence: 99%

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Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer

Topić

Ljujić

Nikolić

et al. 2010

Pathol. Oncol. Res.

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Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer

Topić

Ljujić

Nikolić

et al. 2010

Pathol. Oncol. Res.

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“…It has been shown that a second promoter polymorphism in the MMP‐9 gene (90(CA)14–24) affects blood MMP‐9 levels in healthy adults and obese patients . Furthermore, five polymorphisms in the NE promoter region have been linked to the risk of lung cancer . However, no relationships between the latter polymorphisms and COPD have yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Concomitant elevations of MMP‐9, NGAL, proMMP‐9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease

Bchir

Nasr

Bouchet

et al. 2016

J Cellular Molecular Medi

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A growing body of evidence points towards smoking‐related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase‐9 (pro‐ and active MMP‐9), neutrophil gelatinase‐associated lipocalin (NGAL) and the proMMP‐9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable‐phase COPD patients (82 smokers, 18 never‐smokers) and 28 healthy adults (21 smokers, 7 never‐smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP‐9, NGAL and proMMP‐9/NGAL in COPD smokers. While the triad discriminated between smokers and non‐smokers in the COPD group, MMP‐9 and proMMP‐9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack‐years did not alter the findings. Serum MMP‐9, NGAL and proMMP‐9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP‐3 (but not of IL‐6 and MMP‐12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack‐years. Among COPD smokers, levels of MMP‐9, NGAL and proMMP‐9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP‐9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP‐9, NGAL, proMMP‐9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.

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“…In 6 out of 123 ERSD patients we found PCR (Polymerase Chain Reaction) products with two patterns of DNA fragments: 502bp/397bp and 449bp/397bp ( Figure 1 A). Sequencing of these fragments revealed two duplications in heterozygosity: an extra block composed by the 4th and 5th repetitions of the promoter region between the 5th and 6th repetitions, and an extra 52bp between the 4th and 5th repetitions, respectively (the latter was described in previous studies) [ 4 ]. In the remaining 117 patients, we identified two SNPs already described: c.-741G>A ( Figure 1 B.I–B.III) and c.-903T>G ( Figure 1 C.I,C.II).…”

Section: Resultsmentioning

confidence: 85%

“…Neutrophil elastase, a protease able to degrade several extracellular matrix proteins, is encoded by ELANE gene. Polymorphisms of ELANE gene have been associated with the development of several pathologies [ 4 , 5 , 6 ]. Indeed, the presence of mutations and single nucleotide polymorphisms (SNPs) in the codifying region and in the six repetitive tandem motifs of the promoter appear to influence the level of elastase expression, promoting proteolytic disturbances [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

Fernandes

Freitas

Miranda³

et al. 2016

Genes

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End-stage renal disease (ESRD) patients have a high mortality rate that exceeds that of non-ESRD population. The hemodialysis procedure induces neutrophil activation and elastase release, which might have a role in the inflammatory process and in the development of oxidative stress. The ELANE gene encodes the neutrophil elastase. We analyzed the effect of ELANE promoter region polymorphisms and its relation with the circulating levels of elastase, as well as several clinical, biochemical and inflammatory markers in 123 ESRD patients. We found two duplications in heterozygosity in the promoter region and a new polymorphism, the c.-801G>A. ESRD patients heterozygous for the c.-903T>G polymorphism had no changes in the circulating levels of elastase or other evaluated variables, and those homozygous for the c.-741G>A polymorphism showed significant effects on neutrophils count, as well as in neutrophils/lymphocytes ratio, which might be associated with an increased inflammatory process.

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Polymorphisms in the promoter region of neutrophil elastase gene and lung cancer risk

Cited by 15 publications

References 20 publications

Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer

Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer

Concomitant elevations of MMP‐9, NGAL, proMMP‐9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease

Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

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