血管紧张素转换酶基因多态性与支气管哮喘易感性关系的研究

Polymorphism of angiotensin converting enzyme gene and susceptibility to asthma with familial aggregation

目的 探讨血管紧张素转换酶（ＡＣＥ）基因插入（Ｉｎｓｅｒｔｉｏｎ，Ｉ） 与缺失（ｄｅｌｅｔｉｏｎ，Ｄ） 多态性与支气管哮喘易感性、肺功能间的关系。方法 采用聚合酶链反应（ＰＣＲ）确定５０ 例哮喘患者，７ 个哮喘家系所有个体以及５０ 名正常健康对照者ＡＣＥ的基因型；乙酰甲胆碱（Ｍｃｈ） 激发试验测定气道的反应性；测定哮喘患者肺的通气功能［ 一秒钟用力呼气容积占预计值百分比（ＦＥＶ１ 占预计值％ ） ，一秒钟用力呼气容积／ 用力肺活量（ＦＥＶ１／ＦＶＣ）］。结果 ＡＣＥ 基因Ｄ纯合型在哮喘组及哮喘家系组的频率分别为４６％ 、５３％ ，在对照组为１６％ ，两组比较差异有显著性（ Ｐ＜ ０－０５） ，相对危险度为４－９８。携带Ｄ型纯合子的哮喘患者ＦＥＶ１ 占预计值％ 及ＦＥＶ１／ＦＶＣ的值分别为５７％ 、６９％ ，携带非Ｄ型的哮喘患者其ＦＥＶ１ 占预计值％ 及ＦＥＶ１／ＦＶＣ 的值分别为７４％ 、７９％ ，两组比较差异具有显著性（ Ｐ＜ ０－０５） 。结论提示ＡＣＥ基因Ｄ型纯合子与哮喘的遗传易感性相关，另外ＤＤ基因可能与哮喘患者肺功能损害的程度有关。

Objective Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin II (AT II) and inactivation of bradykinins and tachykinins, which are potent bronchial constrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE Whether or not the polymorphism of ACE gene is associated with asthma and bronchial responsiveness was investigated Methods A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR) Methacholine broncho(Mch) provocation and pulmonary function tests were performed in all asthmatics Results There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46% vs 16%, P <0 05; Odd ratio 4 98) Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (74% vs 57%, P <0 05; 79% vs 69%, P <0 05, respectively) Conclusions The results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma DD genotype of ACE might be a risk factor for the degree of airway obstruction