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).


CONCLUSIONS
The adenine allele of TNF-alpha-238 may reduce the risk and severity of BPD.
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Hutzel Women's Hospital, 4707 St Antoine, Detroit, Michigan 48201, USA. nkazzi@med.wayne.edu
S Nadya J
SN
Kazzi
U Olivia
UO
Kim
Michael W
MW
Quasney
Irina
I
Buhimschi
D001997:Bronchopulmonary Dysplasia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000401:mortality; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha