A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population

Sepsis describes a complex clinical syndrome resulting from a systemic inflammatory response to bacteria. Functional studies in animal models of sepsis have catalogued CXCL2 as a candidate gene for the development of the disease. We hypothesized that CXCL2 polymorphisms may confer susceptibility to sepsis and performed an association study using 178 severe sepsis patients and 357 population-based controls. We selected two polymorphisms from the promoter of the gene (-437A/G and -665(AC)(n)), and analyzed whether haplotypes or single loci were associated with disease susceptibility. An overall test of differentiation showed that haplotype distribution was not different between cases and controls (P = 0.407). Likewise, -437A/G was not associated with disease susceptibility (heterozygote odds ratio (OR) 0.68 (0.47-1.03), and homozygote OR 0.86 (0.56-1.32); P = 0.706). However, for the -665(AC)(n), we found that the 24 +/- 1 repeat alleles were associated with susceptibility ( heterozygote OR 2.82 (1.10-7.24), and homozygote OR 3.65 (1.41-9.43); P = 0.0006). This association remained significant when using a multiple logistic regression analysis (OR 2.23; 95% confidence intervals (95% CI) 1.22-4.03; P = 0.008) and after a genomic control adjustment (P = 0.017). Although replicate studies and functional assays are needed, these results suggest that CXCL2 gene variants may contribute to the development of severe sepsis.