Abstract
Background: A systemic perinatal inflammatory response is known to be a risk factor of severe intraventricular hemorrhage (IVH) in preterm infants. Molecular markers predicting susceptibility to cerebral morbidity in premature infants are missing. Genetic polymorphisms in the tumor necrosis factor (TNF) -gene are known to modify TNF expression.
Aims: To study the incidence of biallelic polymorphisms of the TNF alpha promoter region and NcoI polymorphism of the TNF beta gene in premature infants with severe IVH.
Methods: Study subjects: A double blinded retrospective cohort study was carried out on stored Guthrie blood spot cards. 27 premature infants < 32 weeks of gestational age with sonographic finding of severe IVH at day 7 postnatal age (grade III IVH or IVH with apparent periventricular hemorrhagic infarction) and 102 healthy newborn infants (>32+0 weeks of gestation, no signs of severe IVH on ultrasound examination at 7 days postnatal age) were included in the study. TNF allele distribution of the study population was also compared to cohorts of healthy adult volunteers.
Laboratory investigation: To detect microsatellite nucleotide polymorphism in the TNF gene, polymorphism of the TNF alpha promoter-308 region and NcoI polymorphism of TNF beta gene was assessed using polymerase chain reaction (PCR) followed by melting curve analysis or NcoI digestion.
Results: The overall allele frequency and genotype distribution of the -308 TNF-alpha polymorphism were comparable with values found in controls and no difference was found with regards to gender. The overall incidence of the TNF beta 2 allele was higher in the IVH group compared to the control group (81.5% vs.63.2%; p= 0.01). Allele distribution of a polymorphic site within the TNF beta locus in the male patient group significantly differed from the distribution in the control group (TNF beta 1/2 frequency: 13.3%/86.7% vs. 36.8%/63.2%; p= 0.01). Male patients showed a significantly higher prevalence of the homozygous genotype for the TNF beta 2 allele (80% vs. 44%; p= 0.04).
Conclusion: The study indicates a predominance of the TNF beta 2 allele and genotype of a proinflammatory cytokine like TNF in male gender to be linked to a major neuropathological outcome parameter in premature infants.
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Schueller, A., Stueber, F., Kattner, E. et al. 106 Association of Two Tumor Necrosis Factor Polymorphisms with The Incidence of Severe Intraventricular Hemorrhage in Preterm Infants. Pediatr Res 56, 482 (2004). https://doi.org/10.1203/00006450-200409000-00129
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DOI: https://doi.org/10.1203/00006450-200409000-00129