Tumour necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease

Abstract

Tumour necrosis factor(TNF)-a levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-a gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians.Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood.There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung).It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease. Eur Respir J 2000; 15: 281±284.

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

“…However, it must be underlined that neither study provided any objective verification of the presence (or absence) of emphysema. The negative study reported by HIGHAM et al [8] in British subjects did not use DL,CO as an inclusion criterion, but reported a mean ¡ SEM of 75 ¡ 4% pred in their series of 86 COPD patients, a much less severe impairment than that found in the present series (mean ¡ SD 37 ¡ 12).…”

“…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].…”

“…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].…”

Lack of association between adult asthma and the tumour necrosis factor α-308 polymorphism gene

“…Furthermore, the lack of difference between control smokers and asthmatic smokers suggests that TNFa-308 polymorphism does not make smokers more prone to develop asthma. This observation can be compared with a very recent study by HIGHAM et al [24] showing that this polymorphism was not a risk factor for the susceptibility to chronic obstructive pulmonary disease in European Caucasian smokers.…”

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).…”