title: TNF-alpha promoter polymorphism in relation to TNF-alpha production and clinical status in cystic fibrosis.
abstract: The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector alpha (TNF-alpha). A polymorphism in the promoter region of the TNF-alpha gene at nucleotide 308 relative to the transcription start site may be important in determing the host's TNF-alpha response. The aim of this study was to assess the correlation between a TNF-308 promoter polymorphism, ex vivo TNF-alpha production (before and after lipopolysaccharide (LPS) stimulation), and clinical status [FEV1, weight (z-score), BMI, Shwachman score, incidence of diabetes mellitus, and Pseudomonas aeruginosa infection). Genotyping for the biallelic TNF-308 polymorphism was performed by using a real-time PCR cycler. Patients (homozygous for Delta F 508) were grouped according to genotype (TNF2 carriers, n = 16, median age = 15 yr, female/male = 5/11; TNF1 homozygotes, n = 37, median age = 21 yr, female/male = 18/19). TNF-alpha was measured using a chemiluminescent immunometric assay. There was a trend toward higher TNF-alpha values [median TNF2 carriers vs. TNF1 homozygotes: x = 56 vs. 43.5 pg/ml, n.s. (Mann-Whitney U-test] in those carrying the polymorphism and better lung function results [FEV(1) (%) 81 vs. 65, n.s.]. These differences equalized [TNF2 carriers vs. TNF1 56 vs. 51 pg/ml, n.s.; FEV1 (%) 84 vs. 79, n.s.] after age adjustment (+/- 2 yr, n = 15, median age TNF2 vs. TNF1-17/18 yr). There were no significant differences for TNF values after LPS stimulation and the incidence of diabetes mellitus. The TNF-308 promoter polymorphism does not seem to influence TNF-alpha release in whole blood cells and clinical status.
authors.affiliation: Department of Pediatrics, University of Bonn, Bonn, Germany. e.schmitt.grohe@uni-bonn.de
authors.forename: Sabina
authors.initials: S
authors.lastname: Schmitt-Grohé
authors.forename: Frank
authors.initials: F
authors.lastname: Stüber
authors.forename: Malte
authors.initials: M
authors.lastname: Book
authors.forename: Joachim
authors.initials: J
authors.lastname: Bargon
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Wagner
authors.forename: Christian
authors.initials: C
authors.lastname: Naujoks
authors.forename: Ralf
authors.initials: R
authors.lastname: Schubert
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lentze
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011552:Pseudomonas Infections / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator