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

Objectives: To determine whether the allele frequencies and genotype distribution of an interleukin (IL)-1 beta 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 Tool site within exon 5 of the IL-1 beta 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-1 beta 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.