title: Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.
abstract: OBJECTIVE
  Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples.
  
  
  RESULTS
  At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50-0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05-1.83). For infants born 32-36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34-80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21-14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13-0.76).
  
  
  CONCLUSIONS
  Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.
authors: Discipline of Obstetrics and Gynaecology, The University of Adelaide, South Australia, Australia.
authors: Michael
authors: M
authors: Djukic
authors: Catherine S
authors: CS
authors: Gibson
authors: Alastair H
authors: AH
authors: Maclennan
authors: Paul N
authors: PN
authors: Goldwater
authors: Eric A
authors: EA
authors: Haan
authors: Gai
authors: G
authors: McMichael
authors: Kevin
authors: K
authors: Priest
authors: Gustaaf A
authors: GA
authors: Dekker
authors: William M
authors: WM
authors: Hague
authors: Annabelle
authors: A
authors: Chan
authors: Zbigniew
authors: Z
authors: Rudzki
authors: Phillipa
authors: P
authors: VAN Essen
authors: T Yee
authors: TY
authors: Khong
authors: Mark R
authors: MR
authors: Morton
authors: Enzo
authors: E
authors: Ranieri
authors: Heather
authors: H
authors: Scott
authors: Heather
authors: H
authors: Tapp
authors: Graeme
authors: G
authors: Casey
mesh_terms: D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000235:genetics* / Q000821:virology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D012042:Registries; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014777:Virus Diseases / Q000150:complications*
chemical_list: C508598:IL4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D015847:Interleukin-4