4G/5G Polymorphism of Plasminogen Activator Inhibitor -1 Gene Is Associated with Mortality in Intensive Care Unit Patients with Severe Pneumonia

Abstract

Background Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. Methods The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. Results A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. Conclusions The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.

Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema

“…Hypoxemia, which functions as a stressor, increases the expression of heat-shock proteins, and protects important organs, such as the lungs and the brain, from harm. Previous studies (Sapru et al, 2009;Madách et al, 2010) have reported a correlation between the 4G/5G polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene, and the level of expression of pulmonary edema fluid and PAI-1 in the plasma after lung injury. Patients who express the 4G/4G and 4G/5G genotype showed a significant increase in PAI-1 expression; such patients suffered illnesses and inflammatory reactions of greater intensity, and demonstrated obvious pulmonary edema.…”

Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis

“…A previous study reported that the plasminogen activator inhibitor-1 gene 4G/5G polymorphism may be used as a marker for the diagnosis of Identification of miRNA biomarkers of pneumonia using RNA-sequencing and bioinformatics analysis SAI severe pneumonia (8). Elevated levels of procalcitonin and C-reactive protein are positively correlated with the severity of CAP (9).…”

Гостре Пошкодження Нирок І Тяжка Пневмонія: Сучасна Парадигма Та Клінічні Реалії

“…Сложности в оценке, интерпретации результатов полученных данных, в выборе правильной стратегии коррекции многочисленных факторов, ведущих к развитию ОПП, у каждого конкретного пациента связаны, кроме всего прочего, с генетическими факторами. В частности, в проспективном обсервационном ге-нетическом исследовании описывается 4es/5G по-лиморфизм PAL-1 гена, ассоциированный с ПОД и септическим шоком при пневмонии [20,23].…”