Interleukin-10 -1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

Abstract

IL-10 is an anti-inflammatory cytokine that may have a protective role in acute lung injury. IL-10 expression is affected by a single-nucleotide polymorphism (SNP) located at position -1082 (G to A). The A allele is associated with lower IL-10 production. Low IL-10 production has been linked to the development of BPD. Thus, the IL-10 -1082 SNP may be a genetic risk factor for the development of BPD in the premature newborn. The IL-10 -1082 SNP was determined in 294 (235 African American, 56 Caucasian, and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants and compared to outcome (death and/or development of BPD). Differences in groups were analyzed using ANOVA (continuous variables) or chi square (proportions). The frequency of the A allele in our population was 0.62. Thirty-nine (13.3%) infants were homozygous GG, 146 (49.7%) were heterozygous GA, and 109 (37.0%) were homozygous AA. There were no significant differences between genotype groups with respect to ethnic origin, gender, need for surfactant replacement therapy, and isolation of Ureaplasma urealyticum or Mycoplasma hominis from tracheal aspirates at birth. However, AA infants were slightly more mature and of greater birth weight than GA infants (26.9 +/- 0.2 weeks vs. 26.3 +/- 0.2 weeks, P < 0.05, and 940 +/- 22 g vs. 882 +/- 18 g, P < 0.05, respectively). There was no significant effect of the IL-10 -1082 SNP on mortality or the development of BPD (O2 on 28 days or 36 weeks postconceptional age). However, when considered together, the IL-10 -1082 AA/GA genotypes (lower IL-10 production) were associated with a trend toward reduction in risk for the combined outcome of BPD or death (18/39 vs. 80/255, respectively; P = 0.068). The incidence of other complications of prematurity (retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia) was not different between groups. In conclusion, the IL-10 -1082 G/A SNP does not have a major influence on mortality or the development of BPD in ventilated VLBW infants.