A polymorphism in the tumor necrosis factor-alpha gene promoter region maypredispose to a poor prognosis in COPD

Study objectives: To determine whether the adenine (A)-guanine (G) substitu tion 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. Design: 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 po pulation (n = 99). Patients were followed up prospectively for a period of 2 years. Participants and setting: Participants included 106 COPD patients recruited from a respiratory outpatient clinic and 99 control subjects recruited fro m patients admitted for cardiac catheterization. Measurements and results: DNA was extracted from venous blood, and each sub ject was genotyped for the polymorphism by polymerase chain reaction amplif ication and restriction digestion using Nco1. There was no increased freque ncy of the A allele in patients compared to control subjects. AA homozygous patients had less reversible airflow obstruction (p < 0.05) and a signific antly greater mortality (both all-cause and respiratory deaths) on follow-u p (p < 0.001), despite a shorter cigarette smoking history. Conclusions: This study suggests that homozygosity for this A allele predis poses to more severe airflow obstruction and a worse prognosis in COPD.