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Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma.

ABSTRACT: Peroxiredoxin 6 (PRDX6) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma.To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. In silico modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using in silico modeling. Chi2 analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.This study revealed novel SNPs within the PRDX6 gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of PRDX6 genetic variation in other diseases, where oxidative stress is suspected.

SUBMITTER: Rushefski M

PROVIDER: S-EPMC3121666 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma.

Rushefski Melanie M Aplenc Richard R Meyer Nuala N Li Mingyao M Feng Rui R Lanken Paul N PN Gallop Robert R Bellamy Scarlett S Localio A Russell AR Feinstein Sheldon I SI Fisher Aron B AB Albelda Steven M SM Christie Jason D JD

BMC medical genetics 20110531

<h4>Background</h4>Peroxiredoxin 6 (PRDX6) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma.<h4>Methods</h4>To examine the extent of variation in the PRDX6 gene, we performed direct sequencing of the 5' UTR, exon ...[more]

PMID: 21627785

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Project description:ObjectivesTo assess the incidence, severity, and outcomes of pediatric acute respiratory distress syndrome following trauma using Pediatric Acute Lung Injury Consensus Conference criteria.DesignRetrospective cohort study.SettingLevel 1 pediatric trauma center.PatientsTrauma patients less than or equal to 17 years admitted to the ICU from 2009 to 2017.InterventionsNone.Measurements and main resultsWe queried electronic health records to identify patients meeting pediatric acute respiratory distress syndrome oxygenation criteria for greater than or equal to 6 hours and determined whether patients met complete pediatric acute respiratory distress syndrome criteria via chart review. We estimated associations between pediatric acute respiratory distress syndrome and outcome using generalized linear Poisson regression adjusted for age, injury mechanism, Injury Severity Score, and serious brain and chest injuries. Of 2,470 critically injured children, 103 (4.2%) met pediatric acute respiratory distress syndrome criteria. Mortality was 34.0% among pediatric acute respiratory distress syndrome patients versus 1.7% among patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 3.7; 95% CI, 2.0-6.9). Mortality was 50.0% for severe pediatric acute respiratory distress syndrome at onset, 33.3% for moderate, and 30.5% for mild. Cause of death was neurologic in 60.0% and multiple organ failure in 34.3% of pediatric acute respiratory distress syndrome nonsurvivors versus neurologic in 85.4% of nonsurvivors without pediatric acute respiratory distress syndrome (p = 0.001). Among survivors, 77.1% of pediatric acute respiratory distress syndrome patients had functional disability at discharge versus 30.7% of patients without pediatric acute respiratory distress syndrome patients (p < 0.001), and only 17.5% of pediatric acute respiratory distress syndrome patients discharged home without ongoing care versus 86.4% of patients without pediatric acute respiratory distress syndrome (adjusted relative risk, 1.5; 1.1-2.1).ConclusionsIncidence and mortality associated with pediatric acute respiratory distress syndrome following traumatic injury are substantially higher than previously recognized, and pediatric acute respiratory distress syndrome development is associated with high risk of poor outcome even after adjustment for underlying injury type and severity.

Project description:Acute lung injury following lung resection surgery is not rare and often related to mortality. Although it has been a significant clinical and economic impact associated with increased intensive care unit (ICU) utilization, length of hospital stay, and associated cost, it is unpredictable. Aims of this study were to identify the modifiable risk factors of postoperative acute lung injury (PALI) following lung cancer surgery.We retrospectively analyzed medical records of 354 cases of lung cancer surgery in the tertiary university hospital from January 2012 to December 2015. PALI was defined as bilateral diffuse pulmonary infiltration on chest radiography, oxygenation failure (PaO2/FiO2 < 300), and absence of sign of left ventricular failure within a week from operation. We classified patients into either PALI group or non-PALI group and compared clinical characteristics of two groups. Logistic regression model was fitted to evaluate the risk factor of PALI.Among 354 cases of lung cancer surgeries, 287 lobectomies were analyzed. The overall incidence of PALI was 2.79% (8/287); four patients developed pneumonia with acute respiratory distress syndrome, and four patients developed ALI without clinical infection sign. There was no difference in baseline characteristics between PALI group and non-PALI group, but in operative parameters, a larger amount of fluid infusion was observed in PALI group. Logistic regression model showed underlying ischemic heart disease (OR 7.67, 95% CI 1.21-47.44, P = .03), interstitial lung disease (OR 30.36, 95% CI 2.30-401.52, P = .01), intravascular crystalloid fluid during surgery (OR 1.10, 95% CI 1.00-1.20, P = .04), and intraoperative transfusion (OR 56.4, 95% CI 3.53-901.39, P < .01) were risk factors of PALI. PALI increases ICU admission, use of mechanical ventilator, duration of hospital stay, and mortality.The clinical impact of PALI is marked. Significant independent risk factors have been identified in underlying ischemic heart disease, interstitial lung disease, intravascular crystalloid fluid, and transfusion during surgery.

Project description:OBJECTIVES:To determine risk factors identifiable at hospital arrival associated with acute respiratory distress syndrome development among critically injured children. DESIGN:Retrospective cohort study. SETTING:Level I or II adult or pediatric trauma centers contributing to the National Trauma Data Bank from 2007 to 2016. PATIENTS:Patients less than 18 years admitted to an ICU with traumatic injury. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We determined associations between patient, injury, and clinical characteristics present at hospital arrival with development of acute respiratory distress syndrome recorded as a hospital complication. Acute respiratory distress syndrome occurred in 1.8% of 146,058 critically injured children (n = 2,590). The only demographic factor associated with higher risk of developing acute respiratory distress syndrome on multivariable analysis was African American race (relative risk, 1.42 vs white; 95% CI, 1.13-1.78). Injury characteristics included firearm injuries (relative risk 1.93; 1.50-2.48) and motor vehicle crashes (relative risk, 1.91; 1.57-2.31) relative to falls; spine (relative risk, 1.39; 1.20-1.60), chest (relative risk, 1.36; 1.22-1.52), or lower extremity injuries (relative risk, 1.26; 1.10-1.44); amputations (relative risk, 2.10; 1.51-2.91); and more severe injury (relative risk, 3.69 for Injury Severity Score 40-75 vs 1-8; 2.50-5.44). Clinical variables included abnormal respiratory status (intubated relative risk, 1.67; 1.23-2.26 and hypopnea relative risk, 1.23; 1.05-1.45 and tachypnea relative risk, 1.26; 1.10-1.44) and lower Glasgow Coma Scale score (relative risk, 5.61 for Glasgow Coma Scale score 3 vs 15; 4.44-7.07). CONCLUSIONS:We provide the first description of the incidence of and risk factors for acute respiratory distress syndrome among pediatric trauma patients. Improved understanding of the risk factors associated with acute respiratory distress syndrome following pediatric trauma may help providers anticipate its development and intervene early to improve outcomes for severely injured children.

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Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma.

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Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma.

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