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

Abstract

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.

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

“…A TNF-α gene polymorphism resulting in increased TNF-α levels has also been described in a population that is uniquely susceptible to the development of COPD (Huang et al 1997;Sakao et al 2002), although other studies have not been able to corroborate this fi nding (Higham et al 2000;Ferrarotti et al 2003). Interestingly, serum concentrations of TNF-α, as well as TNF-α secretion by monocytes, is particularly robust in the subset of COPD patients with weight loss or cachexia (Di Francia et al 1994;De Godoy et al 1996;Pitsiou et al 2002).…”

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

“…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). The uncertainty regarding the relationship between the TNF-308G/A polymorphism and TNF-α expression in vivo as well as the possibility of another TNF gene polymorphism of greater functional significance in COPD also need to be considered (Higham et al 2000;Ferrarotti et al 2003).…”

“…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). The uncertainty regarding the relationship between the TNF-308G/A polymorphism and TNF-α expression in vivo as well as the possibility of another TNF gene polymorphism of greater functional significance in COPD also need to be considered (Higham et al 2000;Ferrarotti et al 2003).…”

“…TNFR1 and TNFR2 are type-I membrane ligands on the cell surface for both TNF-α and Lt-α. Both TNF receptors are involved in mediating numerous TNF-α and Lt-α effector functions (Ferrarotti et al 2003).…”

Pathogenic Mechanisms in Emphysema: From Protease Anti-Protease Imbalance to Apoptosis

“…One study compared gene polymorphism in 169 Dutch COPD patients compared with Dutch controls, and reported an increased frequency of the G/A genotype in patients without radiological emphysema (Kucukaycan, M., et al, 2002). Another study from Italy compared 63 male patients with COPD with 86 healthy controls, and found no difference in gene polymorphisms between the two groups (Ferrarotti, I., et al, 2003).…”