Abstract
BackgroundGenetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection.MethodsInfectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs).ResultsThe IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003).ConclusionThe IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.
Highlights
Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection
The purpose of this study was to determine if there is a relationship between the IL-10 -1082 G/A, IL-6 -174 G/C and CD14 -260 C/T single nucleotide polymorphism (SNP) and risk for or outcome from sepsis in mechanically ventilated very low birth weight (VLBW) infants
Late onset blood stream infection (BSI) was the major cause of late mortality in ventilated VLBW infants with 14/15 deaths occurring after 28 days of age directly attributable to BSI (RR 15.3, 95% CI 2.0–117.9; p < 0.001)
Summary
Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection. The incidence of one or more episodes of late onset blood stream infection (BSI) in this population ranges from 25–30% with higher rates for infants with birth weights less than 1000 grams [2,3,4,5]. Genetic variation in the innate immune system of the host may play a role in determining the risk of developing and outcome from infection. Variation in the ability to recognize pathogens may influence the risk of infection. The engagement of CD14 and LPS-binding protein during recognition of Gram-negative bacteria results in activation of a complex of innate host defense mechanisms. The CD14 -260 T allele may increase modify the risk for septic shock [10]
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