title: Haplotypes of tumor necrosis factor gene and tracheal aspirate fluid levels of tumor necrosis factor-alpha in preterm infants.
abstract: Individual variability in the production of tumor necrosis factor-alpha (TNF-alpha) has been attributed to genetic factors. We examined whether alleles of TNF gene (lymphotoxin-alpha+250, TNF-alpha-308, and TNF-alpha-238) affect tracheal aspirate fluid (TAF) levels of TNF-alpha 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-alpha+250, TNF-alpha-308, TNF-alpha-238)] of TNF were correlated with levels of TNF-alpha. Diplotypes of TNF (genotypes of haplotypes) classified as high, intermediate, or low based on their relation to TAF TNF-alpha levels were also correlated with TNF-alpha levels. The most frequent (and reference haplotype) was AGG. The GGG haplotype was associated with the lowest TAF TNF-alpha levels on day 7 among African American infants (p < 0.008). Sequential changes in levels of TNF-alpha 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-alpha. Diplotypes of TNF are associated with fetal chorioamnionitis.
authors.affiliation: Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI 48201, USA. nkazzi@med.wayne.edu
authors.forename: S Nadya J
authors.initials: SN
authors.lastname: Kazzi
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Michael W
authors.initials: MW
authors.lastname: Quasney
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D002821:Chorioamnionitis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012307:Risk Factors; D013396:Suction; D014132:Trachea / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha