TY - JOUR T1 - Association of two tumour necrosis factor gene polymorphisms with the incidence of severe intraventricular haemorrhage in preterm infants JF - Journal of Medical Genetics JO - J Med Genet SP - 604 LP - 608 DO - 10.1136/jmg.2004.021378 VL - 42 IS - 7 AU - A Heep AU - A C Schueller AU - E Kattner AU - M Kroll AU - J Sander AU - M Wisbauer AU - P Bartmann AU - F Stueber Y1 - 2005/07/01 UR - http://jmg.bmj.com/content/42/7/604.abstract N2 - The tumour necrosis factor (TNF) α and β gene pair is located in the human major histocompatibility complex between 6p21.1 and 6p21.3.1,2 Gene polymorphisms within the TNFα and TNFβ gene are well described.3–7 The extent of TNFα expression has been shown to be associated with the overall allele frequency and genotype distribution of the NcoI restriction fragment length polymorphism in the first intron of the TNFβ locus.8,9 In an in vitro endotoxin stimulation model, the extent of TNF expression has been correlated to the genotype of a single base polymorphism in the −308 promoter region of the TNFα gene.10 In contrast to this finding, the clinical importance of polymorphisms in the TNFα gene remains controversial. Survival in severe sepsis11 has not been associated with genotype distribution of single base mutation in the −308 promoter region of the TNFα gene. Focussing on neonatal morbidity, neither the development of chronic lung disease of prematurity12 nor necrotising enterocolitis13 were correlated to genotype distribution of the TNFα gene, whereas the development of intraventricular haemorrhage (IVH) was correlated to the −308 promoter region polymorphism of the TNFα gene.12 Genetic determination of the individual inflammatory response may influence the susceptibility to poor outcome after systemic infection or severe tissue damage.8,9,14 Premature infants are at high risk of cerebral morbidity, which is associated with long term limitations and disability.15 Immaturity as well as a systemic perinatal inflammatory response16–22 play a major role in the pathogenesis of cerebral haemorrhage and white matter brain damage. Molecular markers predicting susceptibility to cerebral morbidity in premature infants are missing and thus prophylactic therapeutic strategies are still limited. The aim of this study was to describe the frequency of two biallelic polymorphisms within the TNF … ER -