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

Abstract

SummaryThe neutrophil elastase (NE) gene encodes a powerful serine protease that is involved in the process of normal tissue turnover, natural host defense or tissue damage in acute and chronic inflammatory disorders. Furthermore, NE was suggested as one of the determinant factors of individual susceptibility to lung cancer resulting from imbalance between α1-antitrypsin (AT) and NE. To determine whether NE plays a role in risk for lung cancer, we screened polymorphisms in the promoter region of the NE gene and assessed the role of the NE polymorphisms in the risk for lung cancer. We confirmed three previously identified polymorphisms which are located at −903, −741, and extra 52 bp STS relative to the transcription initiation site. In addition, two new polymorphisms at −832 (G/T) and −789 (C/T) were identified. Their rare allelic frequencies of new polymorphism are 0.02 and 0.01, respectively, among Caucasians. The prevalence of the NE −903 (T/T) and (T/G) genotypes were 0.88 and 0.12 in controls as compared to 0.96 and 0.04 in lung cancer patients using genomic DNA isolated from 113 Caucasian lung cancer cases and 131 controls. A significant increase in lung cancer risk was observed for expected high NE activity genotypes (OR = 3.2, 95% CI = 1.02-10.3) as compared to low NE activity genotypes. These results were consistent with previous in vitro functional analysis, which reported an approximately two-fold increase enzyme expression with the −903T/−741G allele as compared to the −903G/ −741A variant. These results confirm that the NE promoter region polymorphisms may influence in risk for lung cancer.

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

“…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).…”

“…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].…”

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

“…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.…”

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

“…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).…”

“…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 ].…”