title: Candidate genes and cerebral palsy: a population-based study.
abstract: OBJECTIVE
  The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.
  
  
  METHODS
  A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.
  
  
  RESULTS
  For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.
  
  
  CONCLUSIONS
  Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.
authors.affiliation: Schools of aPaediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Gibson
authors.forename: Alastair H
authors.initials: AH
authors.lastname: Maclennan
authors.forename: Gustaaf A
authors.initials: GA
authors.lastname: Dekker
authors.forename: Paul N
authors.initials: PN
authors.lastname: Goldwater
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sullivan
authors.forename: David J
authors.initials: DJ
authors.lastname: Munroe
authors.forename: Shirley
authors.initials: S
authors.lastname: Tsang
authors.forename: Claudia
authors.initials: C
authors.lastname: Stewart
authors.forename: Karin B
authors.initials: KB
authors.lastname: Nelson
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D015703:Antigens, CD / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000235:genetics*; D000074283:Endothelial Protein C Receptor; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D015997:Neonatal Screening; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011486:Protein C / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D018570:Risk Assessment; D016036:Seroepidemiologic Studies; D013021:South Australia / Q000453:epidemiology
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D015703:Antigens, CD; D002352:Carrier Proteins; D000074283:Endothelial Protein C Receptor; D016209:Interleukin-8; D008565:Membrane Proteins; C478370:PROCR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018343:Receptors, Adrenergic, beta-2; D011956:Receptors, Cell Surface; D052247:Nitric Oxide Synthase Type II