Cytokine polymorphisms linked to cerebral palsy

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Cytokine polymorphisms, one in tumor necrosis factor-alpha (TNF-alpha) and three in separate mannose-binding lectin codons, are linked to an increased risk of cerebral palsy. Alteration in cytokine response to infection in gestation could cause the type of brain damage associated with cerebral palsy, according to Australian researchers.

The study, conducted by Dr. Catherine S. Gibson of The University of Adelaide and colleagues in the South Australian Cerebral Palsy Research Group, involved 443 infants with cerebral palsy and 883 matched controls.

DNA testing showed the risk of developing quadriplegia in a full term infant heterozygous for the TNF-alpha-308 polymorphism was nearly doubled (odds ratio 1.82). The risk of diplegia was more than doubled (odds ratio 2.12) in infants carrying a polymorphism in mannose-binding lectin codon 54, whether the infants were homozygous or heterozygous for the mutation.

Dr. Gibson and colleagues also report in the March American Journal of Obstetrics and Gynecology, that mannose-binding lectin codon-54 increased the risk of diplegia at all gestational ages (odds ratio 1.55). The presence of any polymorphism in exon-1 of mannose-binding lectin roughly doubled the risk of diplegia.

Overall, the presence of any cytokine polymorphism had an odds ratio of 1.37 for cerebral palsy.

The researchers note that cytokines are produced in response to infection. If an infant carries a polymorphism causing susceptibility to overreaction to cytokines, they conclude, that could cause a process in the brain leading to cerebral palsy.