TNF-α+308、TNF-α+489基因态性与慢性阻塞性肺疾病的相关性研究

摘要

Objective It is to investigate the relationship of TNF - α + 308 , TNF - α + 489 genetic polymorphism and environmental factors with chronic obstructive pulmonary disease ( COPD ) occurrence. Methods According to patient s age, gender, and case and control group matched 1:2, case-control study was designed to investigate 180 cases of hospitalized patients with COPD and 360 healthy subjects of the basic information, and the TNF - α + 308, TNF - α + 489 genotype were detected by PCR - RFLP method, using Logistic regression analysis to analyze the relationship between TNF - α + 308, TNF - α + 489 genotype, smoking factors and the COPD, and the interaction between them. Results ① The age, gender difference between case and control groups was not statistically significant, smoking, lung cancer, family history, FEV1/Pre, FEV1/FVC between the two groups was statistically significant. ②TNF - α +308 allele A frequency of case and control group were 15. 6% vs 8. 2% respectively, the risk allele A occured COPD OR was 2. 06 ( 95% Cl( 1. 39 ~ 3. 05 ) ) TNF - α +489 Aallele frequencies of case and control group were 16.1% , 6.9% , TNF-a+489 A allele OR was 2. 55 (95% CI( 1.71 ~3.09)). ③ Based on the dominant genetic model estimates method, TNF - α + 308 ( + ) and smoke factors together increased the risk of the occurrence of COPD, the OR was 5. 36 (95% CI( 2.81 ~ 10.23 )). TNF-a+489( +) and smoke factors together increased the risk of the occurrence of COPD, the OR was 8. 18 ( 95% Cl( 4. 08 ~ 16. 38 ) ). ( 4 ) TNF - α + 308( + ) combined TNF - α +489 ( + ) influenced the COPD, and OR was 4. 02 ( 95% CI( 1. 89 ,8. 52 ) ), higher than the TNF - α + 308 , TNF - α + 489 genotype independent effect. Conclusion TNF - α + 308, TNF - α + 489 polymorphism associated with COPD, and there is an interaction between TNF - α genotype with smoking factor, TNF - α +308 and TNF - α +489 gene polymorphism may increase the risk of COPD in smoking patients.%目的 探讨TNF-α+308、TNF-α+489基因态性及环境因素与慢性阻塞性肺疾病(COPD)发生的相关性.方法 根据患者的年龄、性别,病例组与对照组按1:2配对设计的病例对照研究方法,调查180例住院COPD患者和360例健康体检者的基本信息,并应用PCR-RFLP技术检测研究对象的TNF-α+308、TNF-α+489的基因型,采用Logistic回归分析TNF-α+308、TNF-α+489基因型和吸烟因素与COPD的关系及其两者间的交互作用.结果 ①病例组与对照组患者的年龄、性别差异无统计学意义,吸烟、肺癌家族史、FEV1/Pre、FEV1/FVC 2组间差异有统计学意义.②病例组TNF-α+308的等位基因A频率为15.6%,对照组为8.2%,等位基因A发生COPD的风险OR值为2.06(95%CI(1.39,3.05));病例组与对照组的TNF-α+489的等位基因A频率分别为16.1%和6.9%,TNF-α+489等位基因A发生COPD的风险OR值为2.55(95%CI(1.71,3.09)).③以显性遗传模式估计,TNF-α+308(+)联合吸烟因素发生COPD的OR值5.36(95%CI(2.81,10.23)),TNF-α+489(+)联合吸烟因素发生COPD的OR值为8.18 (95%CI(4.08,16.38)).④TNF-α+308联合TNF-α+489(+)发生COPD的OR值为4.02 (95%CI(1.89,8.52)),高于TNF-α+308、TNF-α+489基因型独立作用.结论 TNF-α+308、TNF-α+489基因多态性与COPD相关,与吸烟因素存在相加正交互作用.TNF-α+308、TNF-α+489基因多态性可增加吸烟患者发生COPD的风险.