Biomedical Engineering Reference
In-Depth Information
B. Candidate genes for COPD
COPD is characterized by a slowly progressive irreversible airflow limitation
that is primarily due to two pathophysiological changes in the lung: periph-
eral airway inflammation and a loss of lung elastic recoil resulting from par-
enchymal destruction (Fig. 1). Many inflammatory cells, mediators, and
enzymes have been implicated, and these offer potential targets for genetic
investigations. It seems certain that there will be a complex interaction
between several different genetic and environmental factors. To date, the
genes that have been implicated in the pathogenesis of COPD are involved
in antiproteolysis, metabolism of toxic substances in cigarette smoke, anti-
oxidation, the inflammatory response to cigarette smoke, and mucociliary
clearance. The genes involved or potentially involved in the pathogenesis
of COPD are summarized in Table 2.
1. Proteolysis-Antiproteolysis
Severe
a
1
-Antitrypsin deficiency:
a
1
-Antitrypsin (
a
1
-AT) is an acute
phase protein synthesized by the hepatocytes and to a lesser extent by
Figure 1
Summary of pathways and possible candidate genes involved in the patho-
genesis of COPD. TNF
a
, tumor necrosis factor
a
; VDBP, vitamin D-binding protein;
IL-I
b
, interleukin 1
b
;
a
1
-AT,
a
1
-antitrypsin;
a
1
-ACT,
a
1
-antichymotrypsin;
a
2
-MG,
a
2
-macrglobulin; MMPs, matrix metalloproteinases; NE, neutrophil elastase; CatG,
cathepsin G; Pr3, proteinase 3; mEH, microsomal epoxide hydrolase; p450,
cytochrome P-450; GST, glutathione S-transferase; HO-1, heme oxygenase-1; ECH,
extracellular matrix.
