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Am. J. Respir. Crit. Care Med., Volume 163, Number 2, February 2001, 420-422

Association of Tumor Necrosis Factor alpha  Gene Promoter Polymorphism with the Presence of Chronic Obstructive Pulmonary Disease

SEIICHIRO SAKAO, KOICHIRO TATSUMI, HIDETOSHI IGARI, YUJI SHINO, HIROSHI SHIRASAWA, and TAKAYUKI KURIYAMA, and the Association of Non-University-Affiliated Pulmonary Specialist Physicians of Chiba University School of Medicine

Departments of Chest Medicine and Molecular Virology, Chiba University School of Medicine, Chiba, Japan

Tumor necrosis factor alpha  (TNF-alpha ), a potent proinflammatory cytokine, may be involved in the development of chronic obstructive pulmonary disease (COPD). The production of TNF-alpha is elevated in the airways of these patients. A polymorphism at position -308 of the TNF-alpha gene promoter (TNF-alpha -308*1/2) is known to be associated with alteration of TNF-alpha secretion in vitro. In this study we examined the differences in TNF-alpha -308*1/2 allele frequency to investigate the association of this polymorphism with the presence of smoking-related COPD. TNF-alpha -308*1/2 allele frequency in 106 patients (73 men and 33 women) was compared with 110 asymptomatic smoker/ex-smoker control subjects matched for sex and age and population control subjects consisting of 129 blood donors. Genotype was analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic DNA isolated from peripheral blood lymphocytes. TNF-alpha -308*1/2 allele frequencies were significantly different among the groups: 0.835/0.165 in patients with COPD, 0.918/0.082 in smoker/ex-smoker control subjects, and 0.922/0.078 in population control subjects. These results indicate that TNF-alpha -308*1/2 alleles are significantly associated with the presence of smoking-related COPD.




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