Document Detail

Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.
MedLine Citation:
PMID:  19566553     Owner:  NLM     Status:  MEDLINE    
AIM: 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). CONCLUSION: 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.
Michael Djukic; Catherine S Gibson; Alastair H Maclennan; Paul N Goldwater; Eric A Haan; Gai McMichael; Kevin Priest; Gustaaf A Dekker; William M Hague; Annabelle Chan; Zbigniew Rudzki; Phillipa VAN Essen; T Yee Khong; Mark R Morton; Enzo Ranieri; Heather Scott; Heather Tapp; Graeme Casey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Australian & New Zealand journal of obstetrics & gynaecology     Volume:  49     ISSN:  1479-828X     ISO Abbreviation:  Aust N Z J Obstet Gynaecol     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-07-01     Completed Date:  2009-10-05     Revised Date:  2009-11-11    
Medline Journal Info:
Nlm Unique ID:  0001027     Medline TA:  Aust N Z J Obstet Gynaecol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  247-53     Citation Subset:  IM    
Discipline of Obstetrics and Gynaecology, The University of Adelaide, South Australia, Australia.
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MeSH Terms
Case-Control Studies
Cerebral Palsy / genetics*,  virology*
Genetic Predisposition to Disease / genetics*
Gestational Age
Infant, Newborn
Interleukin-4 / genetics
Interleukin-6 / genetics
Odds Ratio
Polymorphism, Single Nucleotide / genetics*
Pregnancy Complications, Infectious / virology*
Toll-Like Receptor 4 / genetics
Virus Diseases / complications*
Grant Support
//Medical Research Council
Reg. No./Substance:
0/IL4 protein, human; 0/IL6 protein, human; 0/Interleukin-6; 0/Toll-Like Receptor 4; 207137-56-2/Interleukin-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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