Genetic Factors - What Causes Copd: Smoking Cessation

Content provided by the Faculty of the Harvard Medical School

Genetic factors

There is great interest among researchers in identifying genes that predispose a person to developing chronic obstructive pulmonary disease. To date, one such genetic factor has been identified, although others are likely to be important as well.

A genetic disorder that increases the risk of emphysema is alpha-1-antitrypsin (A1AT) deficiency. This inherited condition involves a defect in the gene that controls the production of A1AT, the protein that neutralizes neutrophil elastase, which degrades lung tissue in emphysema. When the gene is defective, the level of A1AT is about 15% of normal, giving proteases free rein to wreak havoc on the lungs.

Between 75,000 and 100,000 people in the United States have the genetic abnormality that causes A1AT deficiency, but only 20,000 to 40,000 of these people develop emphysema. If you have the genetic defect and you smoke, however, you are virtually certain to get emphysema. In all, A1AT deficiency causes 3% of cases of emphysema. The symptoms usually start around age 30 or 40, as much as a decade earlier than with other types of emphysema.

If you have a close relative with A1AT deficiency, you should have a blood test to screen for the genetic defect. If you have the defect, you can lower your odds of getting emphysema by avoiding tobacco smoke as well as similar irritants such as smoke from wood-burning stoves. You should also be tested if you have symptoms of emphysema in your 30s, or if you show signs of emphysema but have never smoked. If you have the genetic defect and signs of emphysema, your doctor might recommend that you take medication to replace A1AT. Preliminary research suggests that A1AT replacement therapy is most effective for someone with A1AT deficiency who is in the early to middle stages of emphysema and carries the most severe genetic form of the disease.

Other possible genetic causes of COPD are under study. Researchers are examining genes that regulate the production of enzymes that break down oxidants in cigarette smoke. Laboratory techniques that analyze the structure of genes are being used to identify other possible genetic causes of COPD.

Last updated:	May 23, 2007