Tumor Necrosis Factor Gene Complex in COPD and Disseminated Bronchiectasis

Patuzzo, Cristina; Gilè, L. S.; Zorzetto, Michele; Trabetti, Elisabetta; Malerba, G.; Pignatti, Pier Franco; Luisetti, Maurizio

doi:10.1378/chest.117.5.1353

Cited by 56 publications

(37 citation statements)

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“…TNF-a levels are increased in sputum of COPD patients [37], and weight loss in COPD has been associated with increased levels of circulating TNF-a [38]. The potential implications of the two TNF-a and Lt-a polymorphisms investigated have already been extensively discussed [1][2][3][5][6][7][8][9]. In this article, for the first time, the authors have added the genetic study of two other TNF family members, TNFR1 and TNFR2, biologically reasonable candidates involved in mediating a number of TNF-a and LT-a effector functions [19].…”

Section: Discussionmentioning

confidence: 99%

“…For detection of TNF-308 and LtaNcoI polymorphisms in COPD and healthy control populations, the same primers [18] and conditions adopted in previous investigations [7] were used. For the TNFR1 exon 1 polymorphism, the polymerase chain reaction (PCR) conditions were as follows: PCR amplifications were carried out in a total volume of 25 ml containing 100 ng genomic DNA, 0.5 unit Thermus Aqiaticus (Taq) DNA polymerase (Laboratoires Eurobio, Les Ulis Cèdex, France), 0.5 mM of each PCR primer, 1.5 mM MgCl 2 , 200 mM of each dNTP, 67 mM Tris-HCl pH 8.8, 16 mM (NH 4 )SO 4 , and 0.01% Tween.…”

Section: Genetic Analysismentioning

confidence: 99%

“…It was previously reported that the frequency of allele 2 (TNF-308*2), of the biallelic polymorphism located within the promoter region of the TNF-a gene (TNF-308), associated with higher levels of TNF production [4], was significantly higher in the Taiwanese with chronic bronchitis [5] and in the Japanese with COPD [6] than in appropriate controls. In marked contrast, the association with COPD was rejected by similarly planned case-control studies in Italian [7] and British [8] populations and by a longitudinal study focused on decline of lung function within the Lung Health Study in Northern Americans [9].…”

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confidence: 99%

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Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema

Ferrarotti¹,

Zorzetto²,

Beccaria³

et al. 2003

Eur Respir J

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Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). Tumour necrosis factor (TNF) family genes have been widely investigated but inconsistent results may lie either in the genetic heterogeneity of populations or in the poor phenotype definition. A genetic study was performed using a narrower phenotype of COPD.The authors studied 86 healthy smokers and 63 COPD subjects who were enrolled based on irreversible airflow obstruction (forced expiratory volume in one second/forced vital capacity v70% predicted) and a diffusing capacity for carbon monoxide v50% predicted (moderate-to-severe COPD associated with pulmonary emphysema). The following polymorphisms were investigated: TNF-308, the biallelic polymorphism located in the first intron of the lymphotoxin-a gene, and exon 1 and exon 6 of the TNF receptor 1 and 2 genes, respectively.No significant deviations were found concerning the four polymorphisms studied between the two populations.The authors confirm that the tumour necrosis factor family genes, at least for the polymorphisms investigated, are not major genetic risk factors for chronic obstructive pulmonary disease in Caucasians, either defined in terms of emphysema (this study) or airflow obstruction (previous studies). Nevertheless, the authors would like to emphasise the importance of narrowing the phenotype in the search for genetic risk factors in chronic obstructive pulmonary disease. Eur Respir J 2003; 21: 444-449.

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema

Ferrarotti¹,

Zorzetto²,

Beccaria³

et al. 2003

Eur Respir J

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“…In contrast, associations between the TNF2 allele and COPD were not confirmed in other studies, neither in Caucasians (Higham et al 2000;Patuzzo et al 2000), nor in a Japanese population (Ishii et al 2000) (Table 3). There was no association between the TNF-α gene promoter genotype and the severity of airflow obstruction or the degree of emphysema in COPD (Higham et al 2000), neither this genotype played a significant role in bronchiectasis developing as a consequence of frequent respiratory tract infections in COPD patients (Patuzzo et al 2000). A study investigating the -308G/A polymorphism in the TNF-α gene, the LtαNcoI polymorphism in the Lt-α gene, the A/G polymorphism in the TNFR1 gene, and the M/R polymorphism in the TNFR2 gene, did not yield any association between these polymorphisms and a risk for COPD (Ferrarotti et al 2003).…”

Section: Gene Polymorphisms Of Inflammatory Mediators In Relation To mentioning

confidence: 62%

“…Their results indicated that the TNF-α-308 allele 2 might be partly associated with the emphysematous phenotype (Sakao et al 2002). In contrast, associations between the TNF2 allele and COPD were not confirmed in other studies, neither in Caucasians (Higham et al 2000;Patuzzo et al 2000), nor in a Japanese population (Ishii et al 2000) (Table 3). There was no association between the TNF-α gene promoter genotype and the severity of airflow obstruction or the degree of emphysema in COPD (Higham et al 2000), neither this genotype played a significant role in bronchiectasis developing as a consequence of frequent respiratory tract infections in COPD patients (Patuzzo et al 2000).…”

Section: Gene Polymorphisms Of Inflammatory Mediators In Relation To mentioning

confidence: 86%

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

et al. 2008

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20-30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.

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Cytokines

Elias¹,

Homer²

2007

Chronic Obstructive Pulmonary Disease

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Tumor Necrosis Factor Gene Complex in COPD and Disseminated Bronchiectasis

Cited by 56 publications

References 20 publications

Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema

Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Cytokines

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