TNF-alpha promoter polymorphism in relation to TNF-alpha production and clinical status in cystic fibrosis.
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.
Schmitt-Grohé
Sabina
S
Department of Pediatrics, University of Bonn, Bonn, Germany. e.schmitt.grohe@uni-bonn.de
Stüber
Frank
F
Book
Malte
M
Bargon
Joachim
J
Wagner
Thomas O
TO
Naujoks
Christian
C
Schubert
Ralf
R
Lentze
Michael J
MJ
Zielen
Stefan
S
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*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator