Abstract
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.
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Abbreviations
- DQ:
-
Griffiths developmental quotient
- GCA:
-
general cognitive ability, British Ability Scales, 2nd Ed.
- WMD:
-
white matter damage
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Acknowledgements
The authors thank Dr. Linda Hunt, Senior Lecturer in Statistics, Institute of Child Health, University of Bristol, for statistical advice.
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This research was supported by awards from The Southmead Hospital Research Foundation to A.W. and D.H, and The British Heart Foundation (grants RG200015, SP98003, FS01XXX to S.H.E., H.M., and S.D.). The original APIP study was supported by Action Research (grant to N.M.).
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Harding, D., Brull, D., Humphries, S. et al. Variation in the Interleukin-6 Gene Is Associated with Impaired Cognitive Development in Children Born Prematurely: A Preliminary Study. Pediatr Res 58, 117–120 (2005). https://doi.org/10.1203/01.PDR.0000163523.49021.53
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DOI: https://doi.org/10.1203/01.PDR.0000163523.49021.53
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