title: The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy.
abstract: BACKGROUND
  The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population.
  
  
  METHODS
  A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program.
  
  
  RESULTS
  There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis.
  
  
  CONCLUSIONS
  The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.
authors.forename: Dan
authors.initials: D
authors.lastname: Bi
authors.forename: Mingjie
authors.initials: M
authors.lastname: Chen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Honglian
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.forename: Qing
authors.initials: Q
authors.lastname: Shang
authors.forename: Tongchuan
authors.initials: T
authors.lastname: Li
authors.forename: Dengna
authors.initials: D
authors.lastname: Zhu
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Street, 450052 Zhengzhou, China. xingqinghe@hotmail.com.
authors.forename: Qinghe
authors.initials: Q
authors.lastname: Xing
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
mesh_terms: D002547:Cerebral Palsy / Q000097:blood / Q000235:genetics*; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D016207:Cytokines; D015850:Interleukin-6