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Genetic susceptibility to viral exposure may increase the risk of cerebral palsy
Author(s) -
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
Publication year - 2009
Publication title -
australian and new zealand journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.734
H-Index - 65
eISSN - 1479-828X
pISSN - 0004-8666
DOI - 10.1111/j.1479-828x.2009.00999.x
Subject(s) - odds ratio , cerebral palsy , medicine , confidence interval , genetic predisposition , case control study , heterozygote advantage , gestational age , viral meningitis , interleukin 6 , immunology , risk factor , gastroenterology , cytokine , pediatrics , pregnancy , genotype , biology , cerebrospinal fluid , gene , genetics , disease , psychiatry , bacterial meningitis
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.