A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to a poor prognosis in COPD.
OBJECTIVE
To determine whether the adenine (A)-guanine (G) substitution polymorphism at position - 308 on the tumor necrosis factor-alpha gene confers susceptibility to COPD or to the development of a more severe form of disease.


METHODS
A cross-sectional study was undertaken to compare the frequency of the A allele in a group of 106 patients with COPD with that in a control population (n = 99). Patients were followed up prospectively for a period of 2 years.


METHODS
Participants included 106 COPD patients recruited from a respiratory outpatient clinic and 99 control subjects recruited from patients admitted for cardiac catheterization.


RESULTS
DNA was extracted from venous blood, and each subject was genotyped for the polymorphism by polymerase chain reaction amplification and restriction digestion using Nco1. There was no increased frequency of the A allele in patients compared to control subjects. AA homozygous patients had less reversible airflow obstruction (p<0.05) and a significantly greater mortality (both all-cause and respiratory deaths) on follow-up (p<0.001), despite a shorter cigarette smoking history.


CONCLUSIONS
This study suggests that homozygosity for this A allele predisposes to more severe airflow obstruction and a worse prognosis in COPD.
Keatings
V M
VM
Department of Medicine and Therapeutics, University College Dublin, Ireland.
Cave
S J
SJ
Henry
M J
MJ
Morgan
K
K
O'Connor
C M
CM
FitzGerald
M X
MX
Kalsheker
N
N
D000368:Aged; D000483:Alleles; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D004273:DNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha