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 < 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.
Harding
David
D
Department of Child Health, University of Bristol, St. Michael's Hospital, Bristol BS8 2JZ, UK. david.harding@bristol.ac.uk
Brull
David
D
Humphries
Steve E
SE
Whitelaw
Andrew
A
Montgomery
Hugh
H
Marlow
Neil
N
D000483:Alleles; D002675:Child, Preschool; D003071:Cognition; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000235:genetics*; D007361:Intelligence Tests; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008423:Maternal Age; D010865:Pilot Projects; D013997:Time Factors
D015850:Interleukin-6