Association of Tumor Necrosis Factor  α  Gene Promoter  Polymorphism with the Presence of Chronic Obstructive  Pulmonary Disease

Sakao, Seiichiro; Tatsumi, Koichiro; Igari, Hidetoshi; Shino, Yuji; Shirasawa, Hiroshi; Kuriyama, Takayuki

doi:10.1164/ajrccm.163.2.2006031

Cited by 156 publications

(97 citation statements)

References 18 publications

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“…When the present study was planned, it was debated whether inconsistent results in different populations with respect to association of TNF-308*2 allele with COPD was due to a bias related to heterogeneity of COPD patients. In fact, the paper by SAKAO et al [6] reported a positive association with Japanese COPD patients with chronic obstruction in whom a history of chronic bronchitis had been excluded, thus suggesting, even if not clearly stated in the paper, that those patients were mostly affected by emphysema. By contrast, a positive association with the TNF-308*2 allele was found in Taiwanese subjects meeting the criteria for chronic bronchitis [5].…”

Section: Discussionmentioning

confidence: 91%

“…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%

“…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: 91%

Section: Discussionmentioning

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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“…TNF-α has been shown to correlate with body mass index (BMI) and cigarette smoke exposure [71,72] and other inflammatory mediators [73] in COPD. A polymorphism of the promoter region of the TNF-α gene has been implicated in the occurrence, severity, and mortality risk of COPD [74][75][76].…”

Section: Role Of Tnf-α In Asthma and Copdmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

117

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Tumor necrosis factor (TNF)-α, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lung. Given that there is significant literature supporting the pathobiologic role of TNF-α in asthma, mainly in severe refractory asthma, and COPD, TNF-α inhibitors (infliximab, golimumab and etanercept) are now regarded as potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-α inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-α inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-α, perhaps in a more carefully selected patient group. TNF-α treatment should therefore not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-α inhibitors.

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“…Carriage of the TNF2 allele also conferred a higher risk to the development of chronic bronchitis in a Taiwanese population (Huang et al 1997). In the study by Sakao et al (2001), a significant relationship between the TNF1/2 allele frequency and the presence of smoking-related COPD in Japanese was revealed. Sakao et al (2002) subsequently assessed the extent of emphysematous changes in COPD patients using high-resolution CT scanning.…”

Section: Gene Polymorphisms Of Inflammatory Mediators In Relation To mentioning

confidence: 99%

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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Association of Tumor Necrosis Factor α Gene Promoter Polymorphism with the Presence of Chronic Obstructive Pulmonary Disease

Cited by 156 publications

References 18 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

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

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

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