GENETIC MODIFIERS OF THE ALPHA1-ANTITRYPSIN DEFICIENCY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 慢性阻塞性肺疾病（COPD），包括慢性支气管炎和肺气肿，是美国第四大死亡原因1。吸烟是COPD发展的主要危险因素;然而，气流阻塞的发展，COPD的定义特征，在吸烟者之间存在显著差异2。由吸烟解释的肺功能变异的低百分比表明，可能存在对吸烟影响的遗传易感性差异;肺功能的家族聚集性已在一般人群和COPD患者家族中得到证实3，4。 COPD的一个已证实的遗传风险因素是严重的α 1-抗胰蛋白酶（AAT）缺乏症。该方案的主要目标是确定遗传因素，修改谁继承了严重的AAT缺乏症的个人肺部疾病的表达。这项研究将包括核心家庭中所有可用的AAT缺陷兄弟姐妹和任何可用的父母。研究期间不给予研究药物;但是，作为肺功能检查的一部分给予沙丁胺醇。尽管当前研究的重点是AAT缺乏症中肺部疾病的遗传修饰物，但将获得研究参与者的知情同意书，以研究其他AAT相关疾病，包括肝脏疾病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic obstructive pulmonary disease (COPD), which includes chronic bronchitis and emphysema, is the fourth leading cause of mortality in the United States 1. Cigarette smoking is the major risk factor for the development of COPD; however, the development of airflow obstruction, the defining characteristic of COPD, is markedly variable among smokers 2. The low percentage of variance in pulmonary function explained by smoking suggests that differences in genetic susceptibility to the effects of smoking are likely to be present; familial aggregation for pulmonary function has been demonstrated in the general population and in families of COPD patients 3, 4. One proven genetic risk factor for COPD is severe alpha 1-antitrypsin (AAT) deficiency. The primary goal of this protocol is to identify genetic factors that modify the expression of lung disease in individuals who inherit severe AAT deficiency. The study will include all available AAT deficient siblings in a nuclear family and any available parents. There will be no study medication administered during the study; however, albuterol which is given as part of pulmonary function testing. Although the focus of the current study is on the genetic modifiers of lung disease in AAT deficiency, informed consent will be obtained from study participants to investigate other AAT related conditions, including liver disease.