4.6 Article

APOE polymorphism is associated with risk of severe sepsis in surgical patients

Journal

CRITICAL CARE MEDICINE
Volume 33, Issue 11, Pages 2521-2526

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.CCM.0000186368.96146.FB

Keywords

sepsis; polymorphism; genetic; postoperative; human; association study; apolipoprotein E; inflammation

Funding

  1. NIA NIH HHS [R01 AG17556] Funding Source: Medline
  2. NINDS NIH HHS [R21-NS-4487-01, R21 NS4487-0] Funding Source: Medline

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Objective: To test for an association between apolipoprotein E (APOE) genotypes and the occurrence of severe sepsis in an elective surgical cohort. Design: Prospective, observational, single cohort study. Setting: Sixteen-bed surgical intensive care unit (ICU) at a university hospital. Patients: Patients were 343 patients with planned admission to the ICU after major elective noncardiac surgery. Interventions: Blood samples, together with demographic data, baseline clinical data, and Acute Physiology and Chronic Health Evaluation II scores, were collected on admission to the ICU and on each subsequent ICU day. APOE genotyping was conducted using a polymerase chain reaction-based assay. The primary outcome was diagnosis of severe sepsis; secondary outcomes included time on mechanical ventilation, ICU length of stay, and ICU mortality. Measurements and Main Results: Severe sepsis was diagnosed in 34 of 343 patients (9.9%). Carriers of the APO epsilon 3 allele (one or two copies) had a lower incidence of severe sepsis than patients with no APO epsilon 3 allele (p =.014), with a relative risk of 0.284 (95% confidence interval 0.127-0.635). The protective effect of APO epsilon 3 genotype on the incidence of severe sepsis remained significant (p <.01) after adjusting for age, gender, or race in a logistic regression model. Supporting our findings, presence of the APO epsilon 3 allele was also associated with fewer days spent in the ICU (p =.007). In contrast, APOE genotypes were not associated with duration of mechanical ventilation or ICU mortality. Conclusions: In an elective surgical cohort, presence of the APO epsilon 3 allele is associated with decreased incidence of severe sepsis and a shorter ICU length of stay.

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