title: Sequencing of the IL6 gene in a case-control study of cerebral palsy in children.
abstract: BACKGROUND
  Cerebral palsy (CP) is a group of nonprogressive disorders of movement and posture caused by abnormal development of, or damage to, motor control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795, in the promoter region of the interleukin-6 (IL6) gene has been implicated in the pathogenesis of CP by mediating IL-6 protein levels in amniotic fluid and cord plasma and within brain lesions. This SNP has been associated with other neurological, vascular, and malignant processes as well, often as part of a haplotype block.
  
  
  METHODS
  To refine the regional genetic association with CP, we sequenced (Sanger) the IL6 gene and part of the promoter region in 250 infants with CP and 305 controls.
  
  
  RESULTS
  We identified a haplotype of 7 SNPs that includes rs1800795. In a recessive model of inheritance, the variant haplotype conferred greater risk (OR = 4.3, CI = [2.0-10.1], p = 0.00007) than did the lone variant at rs1800795 (OR = 2.5, CI = [1.4-4.6], p = 0.002). The risk haplotype contains one SNP (rs2069845, CI = [1.2-4.3], OR = 2.3, p = 0.009) that disrupts a methylation site.
  
  
  CONCLUSIONS
  The risk haplotype identified in this study overlaps with previously identified haplotypes that include additional promoter SNPs. A risk haplotype at the IL6 gene likely confers risk to CP, and perhaps other diseases, via a multi-factorial mechanism.
authors: Department of Neurology, University of California, 675 Nelson Rising Lane, 94158, San Francisco, CA, USA. pouya.khankhanian@ucsf.edu.
authors: Pouya
authors: P
authors: Khankhanian
authors: Sergio E
authors: SE
authors: Baranzini
authors: Britt A
authors: BA
authors: Johnson
authors: Lohith
authors: L
authors: Madireddy
authors: Dorothee
authors: D
authors: Nickles
authors: Lisa A
authors: LA
authors: Croen
authors: Yvonne W
authors: YW
authors: Wu
mesh_terms: D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000235:genetics*; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6