Variation in the Interleukin-6 Gene Is Associated with Impaired Cognitive Development in Children Born Prematurely: A Preliminary Study

The pro-inflammatory cytokine IL-6 may be neurocytopathogenic, and elevated levels are associated with impaired neurological outcome among children born prematurely. However, the precise mechanisms underlying this association remain unclear. The rare C (rather than G) variant at position –572 in the IL-6 gene is associated with an increased IL-6 synthetic response. If IL-6 mediates cerebral injury, we would anticipate the –572 C allele to be associated with impaired childhood development. We have examined this hypothesis, studying 113 Caucasian children born at ≤32 wk gestation. Cognitive and motor functions were assessed using the Griffiths Developmental Scales at 2 y and British Ability Scales (2nd Ed.) and the ABC Movement Score at 51/2 y. Performance (median, interquartile range) in all three scales was worse in the 10 carriers of the C allele than for those with GG genotype: Griffiths Developmental Quotient: C allele, 92.4 (89.9–96.6) versus CG 100.9 (96.7–104.8), p = 0.002; General Cognitive Ability: C allele, 88.0 (80.3–102.8) versus GG 103.0 (92.0–112.0), p = 0.037; Movement ABC score: C allele 8.3 (6.6–20.3) versus GG 4.0 (1.0–9.5), p = 0.081. The presence of the rare (≥1) IL-6 -572 C-allele (CC+GC genotypes) is associated with impaired cognitive development among children born before 32 wk gestation. These data support a role for IL-6 in the genesis of neurologic impairment in such children.