title: Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants.
abstract: Mutations of genes involved in the innate immune system have been reported to be associated with an increased sepsis rate in adults. We determined the -159T mutation of the CD14 gene, the 896G mutation of the toll-like receptor 4 gene, the 3020insC mutation of the NOD2 gene (NOD2-3020insC), the IL-6 174G/C promoter polymorphism (IL6-174G/C), and the mannose-binding lectin genotype and their association to the subsequent development of neonatal sepsis in a large cohort of very low birth weight (VLBW) infants. Fifty (14%) of 356 VLBW infants developed blood culture-proven sepsis during their stay in the hospital. VLBW infants carrying the NOD2-3020insC allele (n =15) and the IL6-174G allele (n =121) had a significantly higher rate of blood culture-proven sepsis (33% and 19.8%, respectively) than VLBW infants without these genotypes (p = 0.046 and 0.035, respectively). In a multivariate logistic regression analysis, gestational age less than 28 wk (odds ratio, 3.2; 95% confidence interval, 1.7-6.0; p < 0.001) and the homozygous IL6-174G allele (odds ratio, 1.9; 95% confidence interval, 1.0-3.9; p = 0.039) were predictive for the development of sepsis, whereas the NOD2-3020insC allele was only of borderline significance (odds ratio, 3.2; 95% confidence interval, 1.0-10.4; p = 0.052). VLBW infants with repeated episodes of sepsis had higher frequencies of the NOD2-3020insC and IL6-174G allele. The increased sepsis rate of homozygous IL6-174G carriers was especially related to an increase in Gram-positive infections, and was not observed in VLBW infants who received prophylaxis with teicoplanin (frequency of Gram-positive sepsis in homozygous IL6-174G carriers without prophylaxis 16.5% versus 2.4% in homozygous IL6-174G carriers with prophylaxis; p = 0.033).
authors.affiliation: Department of Pediatrics, University of Lübeck, Germany. ahrens@paedia.ukl.mu-luebeck.de
authors.forename: Peter
authors.initials: P
authors.lastname: Ahrens
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kattner
authors.forename: Birgit
authors.initials: B
authors.lastname: Köhler
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Seidenberg
authors.forename: Hugo
authors.initials: H
authors.lastname: Segerer
authors.forename: Jens
authors.initials: J
authors.lastname: Möller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000276:immunology*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D012044:Regression Analysis; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D017334:Teicoplanin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin