GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS IN COPD
| Project/Area Number |
12670548
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
TATSUMI Koichiro Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10207061)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRASAWA Hiroshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (00216194)
KURIYAMA Takayuki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20009723)
IGARI Hidetoshi Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (50312947)
林 文明 千葉大学, 医学部, 助教授 (80173029)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | COPD / TNF-α / smoking / PCR / low attenuation area / polymorphism / emphysema / 慢性閉塞性肺疾患 / 肺気腫 |
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| Research Abstract |
TNF-α may play important roles in airway inflammation and the induction of apoptosis of vascular endothelial cells and/or alveolar epithelial cells in COPD. COPD is a male predominant disease and the production of TNF-α is elevated in the airways of these patients. A polymorphism at the position -308 of the TNF-α gene promoter (TNF1/2) is known to be associated with alteration of TNF-α secretion in vitro. We examined the differences in TNF1/2 allele frequency between men and women, and also between patients with early- and late-onset COPD to investigate the association of this polymorphism with the genetic predisposition to smoking-related COPD. TNF1/2 allele frequency in 106 patients (73 men, 44 patients with early-onset COPD) was compared with 110 asymptomatic smoker/ex-smoker control subjects matched for sex and age. TNF1/2 allele frequencies were significantly different among the groups: 0.835/0.165 in COPD patients, 0.822/0.178 in male patients, 0.807/0.193 in patients with earlyo
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nset COPD, and 0.918/0.082 in smoker/ex-smoker control subjects. These results indicate that TNF1/2 alleles are significantly associated with the genetic predisposition to smoking-related COPD and especially to male patients and patients with early-onset CPE. Alveolar septal cell apoptosis may contribute to the pathogenesis of emphysema. We hypothesized that genotypes containing TNFα allele would show a more destructive emphysematous changes of the lung. The percentage ratio of the low attenuation area to the corresponding lung area (LAA%) was evaluated using a visual scoring system for CT findings in patients with COPD (n=84) and these patients were divided into two groups: those with an LAA% 【less than or equal】 50% and those with an LAA% > 50%. TNF1/2 allele frequency significantly differed between the patients with LAA%【less than or equal】50% (0.896 / 0.104) and those with LAA% > 50% (0.783 / 0.217) (odds ratio = 2.519; 95% CI = 1.06 - 5.97). These results indicate that the TNF-α-308 allele 2 may be associated with the development of emphysematous changes in COPD patients. Less
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Report
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Research Products
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