A Polymorphism in the Tumor Necrosis Factor-α Gene Promoter Region May Predispose to a Poor Prognosis in COPD

Keatings, Vera M.; Cave, Samantha; Henry, Michael J.; Morgan, Kevin; O'connor, Clare M.; FitzGerald, M. X.; Kalsheker, Noor

doi:10.1378/chest.118.4.971

Cited by 101 publications

(61 citation statements)

References 18 publications

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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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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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“…Nine associations from seven studies were available [21,[26][27][28][29], of which one was emphysema [26]. There was no association overall and no association in various stratifications on control group and ethnicity.…”

Section: Meta-analysismentioning

confidence: 99%

Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1

Brøgger

Steen²,

Eiken³

et al. 2006

European Respiratory Journal

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There is evidence of a hereditary component in chronic obstructive pulmonary disease (COPD). A number of genetic association studies have been performed to find susceptibility genes of COPD.The current authors performed a case-control, genetic-association study and a meta-analysis of 16 studies, involving seven polymorphisms in three well-studied genes: microsomal epoxide hydroxylase (EPHX1); tumour necrosis factor; and b 2 -adrenoreceptor. A total of 492 Caucasian smokers and former smokers were recruited from hospital databases and population cohort studies.In the present study, a protective effect of the EPHX1 Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta-analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a pooled OR of 0.5. The same effect has been found in several lung cancer studies. Effects for other candidate SNPs were weak or statistically insignificant, and probable genotyping error was common.In conclusion, the present data and meta-analysis support a role for microsomal epoxide hydroxylase in the aetiology of chronic obstructive pulmonary disease.

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“…Subsequently, many investigators have sought to implicate polymorphisms in TNF in the pathogenesis of COPD. Some of these reports have found an association between polymorphisms of TNF and subgroups of COPD [3][4][5]. However, there are many instances of nonreplication of these associations [6][7][8][9].…”

mentioning

confidence: 99%

Tumour necrosis factor and lymphotoxin A polymorphisms and lung function in smokers

Tanaka

Sandford

Burkett

et al. 2006

European Respiratory Journal

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Genetic variants in the tumour necrosis factor (TNF) gene have been investigated in chronic obstructive pulmonary disease (COPD). However, there are many instances of nonreplication of these associations due to insufficient power or other factors. In this study, a large number of subjects were examined to elucidate whether genetic variations of TNF and/or lymphotoxin A (LTA), which is clustered with TNF, are associated with variations in lung function among smokers.The present authors designed two nested case-control studies in the National Heart, Lung, and Blood Institute Lung Health Study (LHS), which enrolled 5,887 smokers. The first design included continuous smokers who had the fastest (n5279) and the slowest (n5304) decline of lung function during the 5-yr follow-up period, and the second included the subjects who had the lowest (n5533) and the highest (n5532) post-bronchodilator % predicted forced expiratory volume in one second at the start of the LHS. Within the TNF and LTA region, 10 tagging single-nucleotide polymorphisms were selected and genotyped.Unlike the previous associations between TNF-308 and COPD in Asians, the current study found no association between either of the two phenotypes and the LTA and TNF polymorphisms.In conclusion, these results support the findings of previous studies in late-onset chronic obstructive pulmonary disease in Caucasian populations.

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A Polymorphism in the Tumor Necrosis Factor-α Gene Promoter Region May Predispose to a Poor Prognosis in COPD

Cited by 101 publications

References 18 publications

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

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

Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1

Tumour necrosis factor and lymphotoxin A polymorphisms and lung function in smokers

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