Protein C -1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis.

Abstract

OBJECTIVE:

Protein C contains an A/G polymorphism at position -1641 and a C/T polymorphism at -1654 associated with risk of deep venous thrombosis. We tested the hypothesis that these polymorphisms are associated with altered outcome in patients having severe sepsis, in which protein C is a central molecule.

DESIGN:

Prospective cohorts, gene-association study.

SETTING:

Tertiary care medical/surgical intensive care unit.

PATIENTS:

We first recruited a derivation cohort of patients having severe sepsis (n = 62). A second replication cohort was similarly defined but larger (n = 402). We tested for biological plausibility in a third cohort of post-cardiopulmonary bypass patients (n = 61).

INTERVENTIONS:

Patients were genotyped at protein C -1641 and -1654.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome variable was survival in cohorts 1 and 2 and postoperative serum interleukin-6 concentration in cohort 3. Severity of individual organ dysfunctions and systemic inflammation were secondary outcome variables. In the first derivation cohort, the protein C -1641 AA genotype was associated with decreased 28-day survival (p < .05). This finding was confirmed in the much larger replication cohort of patients having severe sepsis (p = .028). In addition, the protein C -1641 AA genotype was associated with significantly more organ dysfunction and more clinical evidence of systemic inflammation (p < .05). Furthermore, the -1641 AA genotype was associated with increased serum interleukin-6 at 4 and 24 hrs after cardiopulmonary bypass (p = .024). There was no association of -1654 A/G with phenotype in any cohort.

CONCLUSIONS:

Protein C -1641 AA genotype is associated with decreased survival, more organ dysfunction, and more systemic inflammation in patients having severe sepsis and with increased interleukin-6 levels after cardiopulmonary bypass surgery.

• Authors: Keith R Walley, James A Russell
• Journal: Critical care medicine (Crit Care Med) Vol. 35 Issue 1 Pg. 12-7 (Jan 2007) ISSN: 0090-3493 [Print] United States
• PMID: 17080006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Protein C

Topics

• APACHE
• Adult
• Aged
• British Columbia (epidemiology)
• Coronary Artery Bypass (adverse effects)
• Female
• Gene Frequency (genetics)
• Genotype
• Hospital Mortality
• Humans
• Interleukin-6 (blood)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Organ Failure (epidemiology, etiology)
• Outcome Assessment, Health Care
• Polymorphism, Restriction Fragment Length
• Promoter Regions, Genetic (genetics)
• Proportional Hazards Models
• Prospective Studies
• Protein C (genetics, metabolism)
• Severity of Illness Index
• Systemic Inflammatory Response Syndrome (blood, complications, genetics, mortality)