Chronic obstructive pulmonary disease (COPD) refers to several different lung conditions, including emphysema and chronic bronchitis, among others, any of which ultimately damage the lungs so that breathing becomes difficult. Because it is not a single disease, there is not “a gene” or even a few genes that “cause” COPD; rather, there are many genetic and environmental factors that interact to determine a person’s susceptibility to COPD.
Alpha-1 Antitrypsin Deficiency
In rare cases, people develop COPD because of a malfunction of an enzyme called alpha-1 antitrypsin. Among other functions, alpha-1 antitrypsin protects the lungs against damage from other proteins. A person who inherits two defective copies of a gene that encodes alpha-1 antitrypsin has a greater risk of developing COPD, especially if exposed to lung irritants such as cigarette smoke, because the lungs lack adequate protection.
The gene PI- also known as SERPINA1- on the long arm of chromosome 14 encodes alpha-1 antitrypsin. Different forms of the PI gene can produce faulty forms of the protein, some of which increase the risk for COPD, including PI-Z and PI-M. People with two mutant copies of PI have from six to 50 times higher an increased risk for COPD, according to Online Mendelian Inheritance in Man (OMIM). On the other hand, these people might never have symptoms or realize that they have the mutation, according to the National Heart, Lung and Blood Institute. OMIM also cites some studies showing that people with only one faulty copy of the gene (heterozygotes) might have a slightly increased risk for COPD.
Other SERPINs
OMIM reports multiple studies that link a region on the long arm of chromosome 2 with COPD. The SERPINE2 gene, a close relative of PI/SERPINA1, lies there, and one group found that certain changes in SERPINE2 occurred more often in people with COPD. However, another group could not replicate those results, so the role of SERPINE2 in COPD is not clear. SERPINA3, another relative of SERPINA1 that lies close to it on the long arm chromosome 14, does not play a role in COPD.
Matrix Metalloproteinases
Genes that encode a class of proteins called matrix metalloproteinases (MMPs) on the long arm of chromosome 11 have been associated with COPD. OMIM reports that people with a particular allele or form of the gene encoding MMP12 are significantly less likely to develop COPD. The MMP1 gene seems to influence the rate of progression of COPD, according to a study cited in OMIM. People with COPD who have a particular type of a genetic difference--called a single nucleotide polymorphism (SNP)--in the MMP1 gene get sicker faster than other people with COPD and normal MMP1 genes.
