A CXCL2 polymorphism is associated with better outcomes in patients with severe sepsis

OBJECTIVE: Several studies have implicated the CXCL2 chemokine as a mediator in the development of sepsis. We hypothesized that a tandem repeat polymorphism (AC)n in the CXCL2 gene, previously associated with susceptibility to severe sepsis, contributes to morbidity and mortality in severe sepsis. DESIGN: Prospective, observational, genetic study of septic patients. SETTING: A network of Spanish postsurgical and critical care units. PATIENTS: A total of 183 critically ill patients fulfilling the International Sepsis Criteria for severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into three groups according to the presence of compound 24 +/- 1 (AC) repeat genotypes: homozygote 24 +/- 1 carriers (HC group), heterozygote 24 +/- 1 carriers (HTC), and non 24 +/- 1 carriers (NC group). Mortality, development of acute respiratory distress syndrome, and number of failing organs were determined for each group. Overall mortality was 46.4%. HC patients had a lower mortality (39.9%) than HTC (52.2%) and NC (72.7%) patients (trend test p = .018). This difference remained significant when using a multiple logistic regression analysis (p = .035). The presence of population stratification was ruled out, since 20 independent genomic control markers demonstrated homogeneity among groups. An exploratory analysis of the effect of acute respiratory distress syndrome on mortality showed a relative risk of 2.60 in the HC group (p = .0004), while in the nonhomozygote carriers (NHC) group the relative risk was 3.34 (p = .0001). CONCLUSIONS: Our data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis. Additional studies are needed to confirm these results.