Genetic variation in complement component 2 of the classical complement pathway is associated with increased mortality and infection: a study of 627 patients with trauma.

Abstract

BACKGROUND:

Trauma is a disease of inflammation. Complement Component 2 (C2) is a protease involved in activation of complement through the classical pathway and has been implicated in a variety of chronic inflammatory diseases. We hypothesized that genetic variation in C2 (E318D) identifies a high-risk subgroup of patients with trauma reflecting increased mortality and infection (ventilator-associated pneumonia [VAP]). Consequently, genetic variation in C2 may stratify patient risk and illuminate underlying mechanisms for therapeutic intervention.

METHODS:

DNA samples from 702 patients with trauma were genotyped for C2 E318D and linked with covariates (age: mean 42.8 years, gender: 74% male, ethnicity: 80% white, mechanism: 84% blunt, injury severity score: mean 25.0, admission lactate: mean 3.13 mEq/L) and outcomes: mortality 9.9% and VAP: 18.5%. VAP was defined by quantitative bronchoalveolar lavage (> 10). Multivariate regression analysis determined the relationship of genotype and covariates to risk of death and VAP. However, patients with injury severity score > or = 45 were excluded from the multivariate analysis, as magnitude of injury overwhelms genetics and covariates in determining outcome.

RESULTS:

Fifty-two patients (8.3%) had the high-risk heterozygous genotype, associated with a significant increase in mortality and VAP.

CONCLUSION:

In 702 patients with trauma, 8.3% had a high-risk genetic variation in C2 associated with increased mortality (odds ratio = 2.65) and infection (odds ratio = 2.00). This variation: (1) identifies a previously unknown high-risk group for infection and mortality; (2) can be determined at admission; (3) may provide opportunity for early therapeutic intervention; and (4) requires validation in a distinct cohort of patients.

• Authors: John A Morris Jr, Cedric Francois, Paul K Olson, Bryan A Cotton, Marshall Summar, Judith M Jenkins, Patrick R Norris, Jason H Moore, Anna E Williams, Brent S McNew, Jeffrey A Canter
• Journal: The Journal of trauma (J Trauma) Vol. 66 Issue 5 Pg. 1265-70; discussion 1270-2 (May 2009) ISSN: 1529-8809 [Electronic] United States
• PMID: 19430225 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C2

Topics

• Adult
• Age Distribution
• Analysis of Variance
• Cause of Death
• Cohort Studies
• Complement C2 (analysis, genetics)
• Complement Pathway, Classical (genetics)
• Cross Infection (diagnosis, genetics, mortality)
• Female
• Genetic Predisposition to Disease (epidemiology)
• Genetic Variation
• Hospital Mortality (trends)
• Hospitals, University
• Humans
• Incidence
• Injury Severity Score
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Pneumonia, Ventilator-Associated (genetics, mortality)
• Prognosis
• Risk Assessment
• Sensitivity and Specificity
• Sex Distribution
• Trauma Centers
• Wounds and Injuries (diagnosis, genetics, mortality)
• Young Adult