PAI-1 Gene Could Be Important Biomarker Of Risk In Patients With Severe Pneumonia

Main Category: Respiratory / Asthma
Also Included In: Infectious Diseases / Bacteria / Viruses;  Genetics;  Clinical Trials / Drug Trials
Article Date: 24 Apr 2009 - 7:00 PDT

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A study published in the May 2009 issue of Anesthesiology offers strong evidence that variations in the plasminogen activator inhibitor (PAI-1) gene are associated with increased time spent on ventilator machines and higher death rates in patients with pneumonia.

Increased levels of PAI-1 are seen in patients with many acute inflammatory lung diseases, including pneumonia.

Being able to identify those who may be most susceptible to adverse effects from lung diseases would be a boon to physicians, said study author Anil Sapru, M.D., M.A.S.

"The results of this study suggest that genetic variations within PAI-1 may help to identify patients at the greatest risk for poor clinical outcomes so that therapeutic and preventive interventions could be directed toward them," he said.

Dr. Sapru and his research group from the University of California, San Francisco sought to understand, among other things, whether elevated PAI-1 activity in pneumonia patients was due to environmental factors, such as severity of illness, or genetic predisposition.

"The regulation of PAI-1 is a complex process and is controlled by metabolic, lifestyle and genetic factors," said Dr. Sapru. "Our study provides additional evidence of the role of PAI-1 in acute lung injury and its relationship to the outcomes of patients with severe pneumonia."

Dr. Sapru's research focused on units within the PAI-1 gene where specific coding sequences called alleles define an individual's genetic makeup.

Alleles exist in pairs within any given gene. Together, these allele pairs are called genotypes. The allele pairs within the PAI-1 gene that Dr. Sapru studied were called 4G and 5G, leading to three possible genotypes: 4G/4G, 5G/5G and 4G/5G genotypes. Pneumonia patients exhibiting 4G/4G and 4G/5G genotypes had higher mortality rates and spent more time on ventilators compared to patients with the 5G/5G genotype.

Of the 111 patients participating in the study, 105 required mechanical ventilation. Patients with the 4G/4G and 4G/5G genotypes averaged only four days off the ventilator after study enrollment, while those with the 5G/5G genotype averaged 13 ventilator-free days.

Thirty two patients died prior to hospital discharge. Of those, 36 percent carried the 4G/5G genotype, 34 percent carried the 4G/4G, and only 8 percent had the 5G/5G genotype.

Anesthesiologists: Physicians providing the lifeline of modern medicine. Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 43,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

Source: American Society of Anesthesiologists (ASA)