title: Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.
abstract: OBJECTIVE
  To determine whether the tumor necrosis factor-α -308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants.
  
  
  METHODS
  Genetic association studies.
  
  
  METHODS
  Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network).
  
  
  RESULTS
  In cohort I, 344 of 1944 (18.2%) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3% for G/G, 15.8% for G/A, 10.0% for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95% confidence interval, 1.03-1.71; G/G vs. A/A: odds ratio, 1.74; 95% confidence interval, 1.06-2.91; p = .03). There was a trend for association of tumor necrosis factor-α -308 A/G genotype with late-onset sepsis episodes (incidence: 17.2% for G/G, 12.5% for G/A, 10.0% for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95% confidence interval, 1.09-1.9; G/G vs. A/A: odds ratio, 2.05; 95% confidence interval, 1.19-3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk.
  
  
  CONCLUSIONS
  No association was found between the tumor necrosis factor-α -308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-α -308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis.
authors.affiliation: Department of Pediatrics and Institute of Medical Biometry and Statistics, University at Lübeck, Germany. haertel@paedia.ukl.mu-luebeck.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Claudia
authors.initials: C
authors.lastname: Hemmelmann
authors.forename: Kirstin
authors.initials: K
authors.lastname: Faust
authors.forename: Corinna
authors.initials: C
authors.lastname: Gebauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoehn
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.forename: Reinhard
authors.initials: R
authors.lastname: Laux
authors.forename: Werner
authors.initials: W
authors.lastname: Nikischin
authors.forename: Hugo
authors.initials: H
authors.lastname: Segerer
authors.forename: Norbert
authors.initials: N
authors.lastname: Teig
authors.forename: Axel
authors.initials: A
authors.lastname: von der Wense
authors.forename: Christian
authors.initials: C
authors.lastname: Wieg
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
mesh_terms: D015331:Cohort Studies; D016001:Confidence Intervals; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000235:genetics* / Q000401:mortality; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D018570:Risk Assessment; D018805:Sepsis / Q000097:blood / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha