Acute lung injury and the coagulation pathway: Potential role of gene polymorphisms in the protein C and fibrinolytic pathways.
There is evidence that dysregulation of coagulation and fibrinolysis may participate in the pathogenesis of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Altered concentrations of several proteins of the coagulation and fibrinolytic pathways in plasma and pulmonary edema fluid from patients with acute lung injury have been related to the severity of lung injury and clinical outcomes. Polymorphisms in the genes encoding for proteins of the protein C and fibrinolysis pathways are known to regulate the production of the respective proteins. It is plausible that these polymorphisms may be associated with the susceptibility to and severity of illness in ALI and ARDS. Well-designed studies that examine the association of these polymorphisms with susceptibility and severity of ALI and ARDS are needed to test the influence of both genetic and environmental factors on the clinical outcomes in patients with ALI and ARDS. There are several important considerations in the design of these genetic association studies, including selection of candidate genes with the most biological plausibility, definition of the phenotype, selection of appropriate controls, determination of the appropriate sample size and assessment of Hardy-Weinberg equilibrium among controls as a measure of internal validity.
Sapru
Anil
A
Pediatric Critical Care Medicine, University of California, 505 Parnassus Avenue, Moffitt 680-B, San Francisco, CA 94143-0106, USA. anil@itsa.ucsf.edu
Wiemels
Joseph L
JL
Witte
John S
JS
Ware
Lorraine B
LB
Matthay
Michael A
MA
D001777:Blood Coagulation / Q000235:genetics*; D005342:Fibrinolysis / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics*; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000503:physiopathology
D011486:Protein C