title: A study of genes encoding cytokines (IL6, IL10, TNF), cytokine receptors (IL6R, IL6ST), and glucocorticoid receptor (NR3C1) and susceptibility to bronchopulmonary dysplasia.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with very preterm birth. The major risk factors include lung inflammation and lung immaturity. In addition, genetic factors play an important role in susceptibility to moderate-to-severe BPD. In this study, the aim was to investigate whether common polymorphisms of specific genes that are involved in inflammation or differentiation of the lung have influence on BPD susceptibility.
  
  
  METHODS
  Genes encoding interleukin-6 (IL6) and its receptors (IL6R and IL6ST), IL-10 (IL10), tumor necrosis factor (TNF), and glucocorticoid receptor (NR3C1) were assessed for associations with moderate-to-severe BPD susceptibility. Five IL6, nine IL6R, four IL6ST, one IL10, two TNF, and 23 NR3C1 single nucleotide polymorphisms (SNPs) were analyzed in very preterm infants born in northern Finland (56 cases and 197 controls) and Canada (58 cases and 68 controls). IL-6, TNF and gp130 contents in umbilical cord blood, collected from very preterm infants, were studied for associations with the polymorphisms. Epistasis (i.e., interactions between SNPs in BPD susceptibility) was also examined. SNPs showing suggestive associations were analyzed in additional replication populations from Finland (39 cases and 188 controls) and Hungary (29 cases and 40 controls).
  
  
  RESULTS
  None of the studied SNPs were associated with BPD nor were the IL6, TNF or IL6ST SNPs associated with cord blood IL-6, TNF and gp130, respectively. However, epistasis analysis suggested that SNPs in IL6ST and IL10 were associated interactively with risk of BPD in the northern Finnish population; however, this finding did not remain significant after correction for multiple testing and the finding was not replicated in the other populations.
  
  
  CONCLUSIONS
  We conclude that the analyzed SNPs within IL6, IL6R, IL6ST, IL10, TNF, and NR3C1 were not associated with BPD. Furthermore, there was no evidence that the studied SNPs directly contribute to the cord blood protein contents.
authors.affiliation: Department of Pediatrics, Institute of Clinical Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. johanna.huusko@oulu.fi.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Huusko
authors.forename: Minna K
authors.initials: MK
authors.lastname: Karjalainen
authors.forename: Mari
authors.initials: M
authors.lastname: Mahlman
authors.forename: Ritva
authors.initials: R
authors.lastname: Haataja
authors.forename: M Anneli
authors.initials: MA
authors.lastname: Kari
authors.forename: Sture
authors.initials: S
authors.lastname: Andersson
authors.forename: Gergely
authors.initials: G
authors.lastname: Toldi
authors.forename: Outi
authors.initials: O
authors.lastname: Tammela
authors.forename: Mika
authors.initials: M
authors.lastname: Rämet
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Lavoie
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D050822:Cytokine Receptor gp130 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004198:Disease Susceptibility; D004843:Epistasis, Genetic; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; C508603:IL6R protein, human; C494199:IL6ST protein, human; D015850:Interleukin-6; C497713:NR3C1 protein, human; D018121:Receptors, Cytokine; D011965:Receptors, Glucocorticoid; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D050822:Cytokine Receptor gp130