TNF-α Promoter Polymorphism in Relation to TNF-α Production and Clinical Status in Cystic Fibrosis

被引:0
|
作者
Sabina Schmitt-Grohé
Frank Stüber
Malte Book
Joachim Bargon
Thomas O. Wagner
Christian Naujoks
Ralf Schubert
Michael J. Lentze
Stefan Zielen
机构
[1] University of Bonn,Departments of Pediatrics
[2] University of Bonn,Department Anesthesiology
[3] University Hospital of Frankfurt,Department of Pulmonary
[4] University Hospital of Frankfurt,Department of Pediatric Pulmonary
[5] Universitätskinderklinik,undefined
来源
Lung | 2006年 / 184卷
关键词
Cystic fibrosis; TNF-α promoter polymorphism; TNF-α plasma levels; FEV; Diabetes mellitus;
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学科分类号
摘要
The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector α (TNF-α). A polymorphism in the promoter region of the TNF-α gene at nucleotide 308 relative to the transcription start site may be important in determing the host’s TNF-α response. The aim of this study was to assess the correlation between a TNF-308 promoter polymorphism, ex vivo TNF-α 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-α was measured using a chemiluminescent immunometric assay. There was a trend toward higher TNF-α 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 [FEV1 (%) 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-α release in whole blood cells and clinical status.
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页码:99 / 104
页数:5
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