title: Gene-gene and gene-environment interactions on IgE production in prenatal stage.
abstract: BACKGROUND
  Prevalence of allergic diseases in children has increased worldwide over the past decades. Allergy sensitization may occur in fetal life. This study investigated whether gene-gene and gene-environment interactions affected cord blood IgE (CBIgE) levels.
  
  
  METHODS
  A total of 575 cord blood DNA samples were subjected to a multiplex microarray for 384 single nucleotide polymorphisms (SNPs) in 159 allergy candidate genes. Genetic association was initially assessed by univariate and multivariate analyses. Multifactor dimensionality reduction (MDR) was used to identify gene-gene and gene-environment interactions. Environmental factors for analysis included maternal atopy, paternal atopy, parental smoking, gender, and prematurity.
  
  
  RESULTS
  Twenty-one SNPs in 14 genes were associated with CBIgE elevation (>or =0.5 KU/l) in univariate analysis. Multivariate analysis identified eleven genes (IL13, IL17A, IL2RA, CCL17, CXCL1, PDGFRA, FGF1, HAVCR1, GNAQ, C11orf72, and ADAM33) which were significantly associated with CBIgE elevation. MDR analyses of gene-gene interactions identified IL13 interacted with IL17A and/or redox genes on CBIgE elevation with the prediction accuracy of 62.52%. Analyses of gene-environment interactions identified that maternal atopy combined with IL13, rs1800925 and CCL22, rs170359 SNPs had the highest prediction accuracy of 67.15%. All the high and low risk classifications on gene-gene and gene-environment interactions by MDR analyses could be validated by Chi-square test.
  
  
  CONCLUSIONS
  Gene-gene (e.g. immune and redox genes) and gene-environment (e.g. maternal atopy and FGF1or redox genes) interactions on IgE production begin in prenatal stage, suggesting that prevention of IgE-mediated diseases may be made possible by control of maternal atopy and redox responses in prenatal stage.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, No. 123 Ta-Pei Road, Kaohsiung, Taiwan.
authors.forename: K D
authors.initials: KD
authors.lastname: Yang
authors.forename: J-C
authors.initials: JC
authors.lastname: Chang
authors.forename: H
authors.initials: H
authors.lastname: Chuang
authors.forename: H-M
authors.initials: HM
authors.lastname: Liang
authors.forename: H-C
authors.initials: HC
authors.lastname: Kuo
authors.forename: Y-S
authors.initials: YS
authors.lastname: Lee
authors.forename: T-Y
authors.initials: TY
authors.lastname: Hsu
authors.forename: C-Y
authors.initials: CY
authors.lastname: Ou
mesh_terms: D054422:Chemokine CCL22 / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005333:Fetus / Q000276:immunology*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000235:genetics*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012907:Smoking
chemical_list: C515482:CCL22 protein, human; D054422:Chemokine CCL22; D018793:Interleukin-13; D007073:Immunoglobulin E