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- Title
Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.
- Authors
Djukic, Michael; Gibson, Catherine S.; MacLennan, Alastair H.; Goldwater, Paul N.; Haan, Eric A.; McMichael, Gai; Priest, Kevin; Dekker, Gustaaf A.; Hague, William M.; Chan, Annabelle; Rudzki, Zbigniew; Van Essen, Phillipa; Khong, T. Yee; Morton, Mark R.; Ranieri, Enzo; Scott, Heather; Tapp, Heather; Casey, Graeme
- Abstract
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.
- Subjects
CEREBRAL palsy; INTERLEUKIN-4; INTERLEUKIN-6; CYTOKINES; GENETIC polymorphisms; INFLAMMATORY mediators; GESTATIONAL age; PEOPLE with quadriplegia; DISEASE risk factors
- Publication
Australian & New Zealand Journal of Obstetrics & Gynaecology, 2009, Vol 49, Issue 3, p247
- ISSN
0004-8666
- Publication type
Article
- DOI
10.1111/j.1479-828X.2009.00999.x