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Härtel, C. et al.

Christoph Härtel, Claudia Hemmelmann, Kirstin Faust, Corinna Gebauer, Thomas Hoehn, Angela Kribs, Reinhard Laux, Werner Nikischin, Hugo Segerer, Norbert Teig, Axel von der Wense, Christian Wieg, Egbert Herting, Wolfgang Göpel,

Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.

OBJECTIVES: 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. DESIGN: Genetic association studies. SETTING: 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). MEASUREMENTS AND MAIN 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.[1]

References

Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants. Härtel, C., Hemmelmann, C., Faust, K., Gebauer, C., Hoehn, T., Kribs, A., Laux, R., Nikischin, W., Segerer, H., Teig, N., von der Wense, A., Wieg, C., Herting, E., Göpel, W. Crit. Care Med. (2011) [Pubmed]

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