Haplotypes of tumor necrosis factor gene and tracheal aspirate fluid levels of tumor necrosis factor-α in preterm infants

Individual variability in the production of tumor necrosis factor-α (TNF-α) has been attributed to genetic factors. We examined whether alleles of TNF gene (lymphotoxin-α+250, TNF-α-308, and TNF-α-238) affect tracheal aspirate fluid (TAF) levels of TNF-α among preterm infants at risk of bronchopulmonary dysplasia. TAF samples were collected within 48 h of birth and 7, 14, 21, and 28 d later. Haplotypes [designated using the nucleotide bases in the chromosome order (lymphotoxin-α+250, TNF-α-308, TNF-α-238)] of TNF were correlated with levels of TNF-α. Diplotypes of TNF (genotypes of haplotypes) classified as high, intermediate, or low based on their relation to TAF TNF-α levels were also correlated with TNF-α levels. The most frequent (and reference haplotype) was AGG. The GGG haplotype was associated with the lowest TAF TNF-α levels on day 7 among African American infants (p < 0.008). Sequential changes in levels of TNF-α correlated with infants' diplotype status [high (HH), intermediate (HL), low (LL)]. Fetal chorioamnionitis but not bronchopulmonary dysplasia was associated with infants' diplotypes (p < 0.005). Haplotypes of the TNF gene influence TAF levels of TNF-α. Diplotypes of TNF are associated with fetal chorioamnionitis.