Genetic susceptibility to viral exposure may increase the risk of cerebral palsy
Article first published online: 15 JUN 2009
© 2009 The Authors. Journal compilation © 2009 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists
Australian and New Zealand Journal of Obstetrics and Gynaecology
Volume 49, Issue 3, pages 247–253, June 2009
How to Cite
DJUKIC, M., GIBSON, C. S., MacLENNAN, A. H., GOLDWATER, P. N., HAAN, E. A., McMICHAEL, G., PRIEST, K., DEKKER, G. A., HAGUE, W. M., CHAN, A., RUDZKI, Z., VAN ESSEN, P., KHONG, T. Y., MORTON, M. R., RANIERI, E., SCOTT, H., TAPP, H. and CASEY, G. (2009), Genetic susceptibility to viral exposure may increase the risk of cerebral palsy. Australian and New Zealand Journal of Obstetrics and Gynaecology, 49: 247–253. doi: 10.1111/j.1479-828X.2009.00999.x
- Issue published online: 15 JUN 2009
- Article first published online: 15 JUN 2009
- Received 24 July 2008; accepted 5 February 2009.
- cerebral palsy;
- Toll-like receptor 4
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.