Polymorphism of tumor necrosis factor-alpha and risk and severity of bronchopulmonary dysplasia among very low birth weight infants.

BACKGROUND Preterm infants with bronchopulmonary dysplasia (BPD) exhibit prolonged elevation of inflammatory indices in their tracheal aspirates. Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of the inflammatory response. The adenine-containing alleles of TNF-alpha-308 and lymphotoxin-alpha+250 have been associated with increased levels of TNF-alpha, whereas the adenine allele of TNF-alpha-238 produces lower levels of TNF-alpha after stimulation. High levels of TNF-alpha may promote chronic inflammation by overwhelming counter-regulatory mechanisms and may lead to the development of BPD. Low levels of TNF-alpha may decrease the risk and/or severity of BPD. OBJECTIVE To determine whether alleles of TNF-alpha play a role in the susceptibility and/or severity of BPD among very low birth weight infants. METHODS Infants with birth weights of < or =1250 g were included. Genotypic analyses (polymerase chain reaction-restriction fragment length polymorphism assays) were performed with DNA extracted from whole-blood samples. RESULTS Infants who developed BPD (fraction of inspired oxygen at postconceptional age of 36 weeks of >0.21, n = 51) had a younger gestational age (mean +/- SD: 27 +/- 4 vs 29 +/- 2 weeks) and lower birth weight (853 +/- 184 vs 997 +/- 193 g) than did infants without BPD (n = 69). The genotypic distributions of lymphotoxin-alpha+250 and TNF-alpha-308 were comparable among the groups of infants. However, the AA and GA TNF-alpha-238 genotypes were much less likely to occur among infants with BPD than among infants without BPD. The adenine allele of TNF-alpha-238 was absent among infants with severe BPD and occurred significantly less often among infants with moderate or severe BPD, compared with infants with mild BPD. The number of adenine alleles of TNF-alpha-238 was correlated inversely with the severity of BPD (r = -.341). CONCLUSION The adenine allele of TNF-alpha-238 may reduce the risk and severity of BPD.