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Variation in the interleukin-6 gene is associated with impaired cognitive development in children born prematurely: a
David Harding1, David Brull, Steve E Humphries
1Department of Child Health, University of Bristol, St. Michael's Hospital, Bristol BS8 2JZ, UK. david.harding@bristol.ac.uk
Insights
The rare C allele in the Interleukin-6 (IL-6) gene is linked to poorer cognitive and motor development in premature infants. This suggests IL-6 may contribute to neurological impairment in these children.
Area of Science:
- Neuroscience
- Genetics
- Developmental Pediatrics
Background:
- Elevated pro-inflammatory cytokine Interleukin-6 (IL-6) is linked to adverse neurological outcomes in premature infants.
- The exact mechanisms connecting IL-6 to cerebral injury in preterm neonates are not fully understood.
- A rare variant (-572 C allele) in the IL-6 gene is associated with higher IL-6 production.
Purpose of the Study:
- To investigate if the IL-6 -572 C allele is associated with impaired cognitive and motor development in Caucasian children born prematurely.
- To determine if IL-6 plays a role in the neurological deficits observed in preterm infants.
Main Methods:
- Studied 113 Caucasian children born at or before 32 weeks gestation.
- Assessed cognitive and motor functions at 2 years using Griffiths Developmental Scales.
- Evaluated cognitive abilities and motor skills at 5.5 years using British Ability Scales and the Movement ABC Score.
Main Results:
- Children carrying the IL-6 -572 C allele showed significantly worse performance on all developmental assessments compared to those with the GG genotype.
- Specifically, carriers of the C allele had lower Griffiths Developmental Quotients (p=0.002) and General Cognitive Ability scores (p=0.037).
- A trend towards poorer motor function was observed in C allele carriers (Movement ABC score, p=0.081).
Conclusions:
- The presence of the IL-6 -572 C allele is associated with impaired cognitive development in preterm infants (<32 weeks gestation).
- These findings support a role for IL-6 in the development of neurological impairments in this vulnerable population.
- Further research into IL-6's neurocytopathogenic effects is warranted.
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 < or =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 (> or =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.
