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

Study on the relationship between TNF-α +308,TNF-α +489 gene polymorphism and chronic obstructive pulmonary disease

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。

Objective It is to investigate the relationship of TNF - α ＋ 308, TNF - α＋ 489 genetic polymorphism and en- vironmental factors with chronic obstructive pulmonary disease （COPD） occurrence. Methods According to patient＇s age, gen- der, 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, FEV/Pre, FEV1/FVC be- tween the two groups was statistically significant. （2）TNF-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% CI （ 1.39 - 3.05 ） ） TNF - α＋ 489 Aallele frequencies of case and control group were 16.1% , 6.9% , TNF -α ＋ 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 - α ＋489 （ ＋ ） and smoke factors together in- creased the risk of the occurrence of COPD, the OR was 8.18 （95% CI（4.08 - 16.38） ）. （4） TNF - α ＋ 308（ ＋ ） com- binedTNF-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 -αgenotype with smoking factor, TNF -α ＋ 308 and TNF -α ＋ 489 gene polymorphism may increase the risk of COPD in smoking patients.