title: Association of interleukin-10 promoter polymorphism with the incidence of multiple organ dysfunction following major trauma: results of a prospective pilot study.
abstract: A dysbalanced immune response is thought to account for a substantial part of the morbidity and mortality after severe trauma. The cytokine interleukin-10 (IL-10) suppresses the transcription of proinflammatory cytokines, mainly in macrophages and monocytes. The objectives of this prospective study in a level I trauma center in Germany were to examine the distribution of IL-10 promoter polymorphisms in a cohort of severely injured patients, to measure IL-10 cytokine levels and relate these to the genotype, and to identify associations of IL-10 polymorphisms with the incidence of severe multiple organ dysfunction syndrome (MODS). The genotypes of polymorphisms -592 and -1082 were determined by polymerase chain reaction (PCR) and restriction cleavage with Rsa 1 or Mnl I, respectively. We analyzed 119 severely injured trauma patients [mean Injury Severity Score (ISS) 38.0 +/- 13.2]. The frequency of the -1082A allele was 0.542, and that of the -592C allele was 0.807. IL-10 polymorphisms were not significantly associated with mean systemic IL-10 cytokine levels 6, 12, and 18 h after admission to the ICU. Carriers of the genotype -592AC had significantly higher overall MOD scores than non-AC carriers (P = 0.018; P(corr) = 0.036). The genotypes of the IL-10 SNP -1082 were not significantly associated with MOD scores. A multivariate Cox hazard regression analysis including important factors of the patients' anatomic and physiological trauma impact revealed only the shock index, the severity of the head injury, and the IL-10 -592 genotype AC as significant independent risk factors for the development of MODS. In this multivariate analysis, carriers of the genotype -592AC displayed a 3.3-fold increase in the relative risk of developing a MODS (P = 0.008, hazard ratio 3.29, 95% CI 1.36-7.97). Our data suggest a possible link between the AC genotype of the -592 single nucleotide polymorphism and significantly higher mean MOD scores. The AC genotype was associated in multivariate analysis with a higher relative risk of MODS in multiply injured patients. Further investigations in larger cohorts need to focus on the potential diagnostic and therapeutic options of this SNP.
authors.affiliation: Department of Trauma Surgery, Ernst-Moritz-Arndt-University of Greifswald, Germany.
authors.forename: Ove
authors.initials: O
authors.lastname: Schröder
authors.forename: Reinhold Alexander
authors.initials: RA
authors.lastname: Laun
authors.forename: Burkhard
authors.initials: B
authors.lastname: Held
authors.forename: Axel
authors.initials: A
authors.lastname: Ekkernkamp
authors.forename: Klaus-Martin
authors.initials: KM
authors.lastname: Schulte
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology* / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D044465:White People / Q000235:genetics; D014947:Wounds and Injuries / Q000150:complications* / Q000235:genetics
chemical_list: D016753:Interleukin-10