GENETIC MODIFIERS OF THE ALPHA1-ANTITRYPSIN DEFICIENCY

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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.