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

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Abstract

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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Authors and Affiliations

  1. Departments of Pediatrics, University of Bonn, Bonn, Germanye

    Sabina Schmitt-Grohé, Christian Naujoks & Michael J. Lentze

  2. Department Anesthesiology, University of Bonn, Bonn, Germany

    Frank Stüber & Malte Book

  3. Department of Pulmonary, University Hospital of Frankfurt, Frankfurt, Germany

    Joachim Bargon & Thomas O. Wagner

  4. Department of Pediatric Pulmonary, University Hospital of Frankfurt, Frankfurt, Germany

    Ralf Schubert & Stefan Zielen

  5. Universitätskinderklinik, Adenauerallee 119, 53113, Bonn, Germany

    Sabina Schmitt-Grohé

Authors
  1. Sabina Schmitt-Grohé
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  2. Frank Stüber
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  3. Malte Book
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  4. Joachim Bargon
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  5. Thomas O. Wagner
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  6. Christian Naujoks
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  9. Stefan Zielen
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Correspondence to Sabina Schmitt-Grohé.

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Schmitt-Grohé, S., Stüber, F., Book, M. et al. TNF-α Promoter Polymorphism in Relation to TNF-α Production and Clinical Status in Cystic Fibrosis. Lung 184, 99–104 (2006). https://doi.org/10.1007/s00408-005-2568-x

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  • DOI: https://doi.org/10.1007/s00408-005-2568-x

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