Association of two tumour necrosis factor gene polymorphisms with the incidence of severe intraventricular haemorrhage in preterm infants

Abstract

There are no molecular markers predicting susceptibility to cerebral morbidity in premature infants and therapeutic strategies are still limited. Genetic polymorphisms in the tumour necrosis factor (TNF) gene modify TNF expression. A systemic perinatal inflammatory response is known to be a risk factor for severe intraventricular haemorrhage (IVH) in preterm infants. We studied the frequency of biallelic polymorphisms of the TNFα promoter region and the Ncol polymorphism of the TNFβ gene in premature infants with severe IVH. The overall allele frequency and genotype distribution of the -308 TNFα polymorphism were comparable with values found in controls. The overall incidence of the TNFβ2 allele was higher in the IVH group compared to the control group. Genotype distribution of a polymorphic site within the TNFβ locus in the male patient group significantly differed from distribution in the control group. Male patients showed a significantly higher prevalence of the homozygous genotype for the TNFβ2 allele. Our study results provide the first molecular link between TNFβ gene polymorphism and the incidence of severe IVH in preterm infants.