Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis.

OBJECTIVES

To determine whether the allele frequencies and genotype distribution of an interleukin (IL)-1beta TaqI polymorphism and an interleukin-1 receptor antagonist polymorphism are associated with susceptibility to and outcome of severe sepsis. In addition, we analyze a possible linkage disequilibrium between a previously described NcoI polymorphism within the tumor necrosis factor (TNF) locus and the two IL-1 gene family polymorphisms.

DESIGN

Prospective, consecutive entry study of patients with diagnosis of severe sepsis.

SETTING

Intensive care unit (ICU) of a university hospital.

PATIENTS

Ninety-three patients with diagnosis of severe sepsis admitted to the ICU between June 1993 and June 1996.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

The polymorphic region within intron 2 of the IL-1ra gene containing variable numbers of a tandem repeat of 86 base pairs was amplified by means of the polymerase chain reaction. Alleles A1-5 are identified according to the size of the amplified DNA product. The region that contains the biallelic TaqI site within exon 5 of the IL-1beta gene was analyzed by polymerase chain reaction amplification and subsequent digestion using the TaqI restriction enzyme. A NcoI TNF-beta polymorphism was determined. The allele frequency of the allele IL-1raA2 was increased in 93 patients with severe sepsis compared with normal individuals (p < .01). No association with patients' outcome was observed. Allele frequencies or genotype distribution of the IL-1beta TaqI polymorphism did not differ between patients and controls. In addition, the allele TNFB2 of the NcoI TNF-beta polymorphism was associated with nonsurvival. Occurrence of the TNFB1 and TNFB2 alleles and genotypes was unrelated to alleles and genotypes of the two IL-1 gene family polymorphisms.

CONCLUSION

In contrast to the TNF-beta NcoI polymorphism, which has been associated with patients' nonsurvival, the allele IL-1raA2 of the polymorphism within the intron 2 of IL-1ra may contribute to susceptibility to sepsis.