Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants

被引:99
作者
Ahrens, P
Kattner, E
Köhler, B
Härtel, C
Seidenberg, J
Segerer, H
Möller, J
Göpel, W
机构
[1] Med Univ Lubeck, Dept Pediat, D-23538 Lubeck, Germany
[2] Childrens Hosp Bult, D-30173 Hannover, Germany
[3] Univ Marburg, Dept Pediat, D-35037 Marburg, Germany
[4] Elisabeth Kinderkrankenhaus, D-26133 Oldenburg, Germany
[5] Childrens Hosp St Hedwig, D-93049 Regensburg, Germany
[6] Childrens Hosp Saarbrucken, D-66026 Saarbrucken, Germany
关键词
D O I
10.1203/01.PDR.0000112100.61253.85
中图分类号
R72 [儿科学];
学科分类号
100202 [儿科学];
摘要
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 CD 14 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).
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页码:652 / 656
页数:5
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