PMID- 19566553
OWN - NLM
STAT- MEDLINE
DCOM- 20091005
LR  - 20220316
IS  - 1479-828X (Electronic)
IS  - 0004-8666 (Linking)
VI  - 49
IP  - 3
DP  - 2009 Jun
TI  - Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.
PG  - 247-53
LID - 10.1111/j.1479-828X.2009.00999.x [doi]
AB  - 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.
FAU - Djukic, Michael
AU  - Djukic M
AD  - Discipline of Obstetrics and Gynaecology, The University of Adelaide, South 
      Australia, Australia.
FAU - Gibson, Catherine S
AU  - Gibson CS
FAU - Maclennan, Alastair H
AU  - Maclennan AH
FAU - Goldwater, Paul N
AU  - Goldwater PN
FAU - Haan, Eric A
AU  - Haan EA
FAU - McMichael, Gai
AU  - McMichael G
FAU - Priest, Kevin
AU  - Priest K
FAU - Dekker, Gustaaf A
AU  - Dekker GA
FAU - Hague, William M
AU  - Hague WM
FAU - Chan, Annabelle
AU  - Chan A
FAU - Rudzki, Zbigniew
AU  - Rudzki Z
FAU - VAN Essen, Phillipa
AU  - VAN Essen P
FAU - Khong, T Yee
AU  - Khong TY
FAU - Morton, Mark R
AU  - Morton MR
FAU - Ranieri, Enzo
AU  - Ranieri E
FAU - Scott, Heather
AU  - Scott H
FAU - Tapp, Heather
AU  - Tapp H
FAU - Casey, Graeme
AU  - Casey G
LA  - eng
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Aust N Z J Obstet Gynaecol
JT  - The Australian & New Zealand journal of obstetrics & gynaecology
JID - 0001027
RN  - 0 (IL4 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Toll-Like Receptor 4)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Case-Control Studies
MH  - Cerebral Palsy/*genetics/*virology
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Gestational Age
MH  - Humans
MH  - Infant, Newborn
MH  - Interleukin-4/genetics
MH  - Interleukin-6/genetics
MH  - Odds Ratio
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Pregnancy
MH  - Pregnancy Complications, Infectious/*virology
MH  - Registries
MH  - Toll-Like Receptor 4/genetics
MH  - Virus Diseases/*complications
EDAT- 2009/07/02 09:00
MHDA- 2009/10/06 06:00
CRDT- 2009/07/02 09:00
PHST- 2009/07/02 09:00 [entrez]
PHST- 2009/07/02 09:00 [pubmed]
PHST- 2009/10/06 06:00 [medline]
AID - AJO999 [pii]
AID - 10.1111/j.1479-828X.2009.00999.x [doi]
PST - ppublish
SO  - Aust N Z J Obstet Gynaecol. 2009 Jun;49(3):247-53. doi: 
      10.1111/j.1479-828X.2009.00999.x.