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Inhibitor kappa B-alpha (IκB-α) promoter polymorphisms in UK and Dutch sarcoidosis

Genes & Immunity volume 4, pages 450–454 (2003)Cite this article

Abstract

The aetiology of sarcoidosis is uncertain; current thinking implicates exposure of genetically susceptible hosts to environmental factors. The nuclear factor kappa B (NF-κB) family of transcription factors are critical regulators of immediate transcriptional responses in inflammatory situations and immune responses. Inhibitor kappa B-alpha (IκB-α) inhibits NF-κB and plays a major role in controlling its activity. We investigated IκB-α promoter polymorphisms using sequence-specific primer-polymerase chain reaction, at positions −881 (A/G), −826 (C/T), and −297 (C/T) in Caucasian sarcoidosis patients (UK and Dutch [NL]), each with their own controls. Disease severity at presentation was assigned using chest radiography and pulmonary function indices. In the combined populations, the −297T allele carriage was more prevalent in patients than in controls (P=0.008). Three common haplotypes were found, of which haplotype 2 (GTT) was significantly associated with sarcoidosis in comparison with control subjects (P=0.01). Subgroup analysis revealed that the −826T allelic carriage was most prevalent in stage II disease, and more prevalent in stage III than in stage IV (P=0.01). The −826T allelic carriage did not show any association with lung function. These results indicate that the NF-κB activation pathway might be associated with the inflammation of sarcoidosis.

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Authors and Affiliations

  1. Clinical Genomics Group, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, UK

    A Abdallah, H Sato, J C Grutters, S Veeraraghavan, A U Wells, R M du Bois & K I Welsh

  2. Department of Pulmonology, Heart Lung Center Utrecht, Sint Antonius Hospital, Nieuwegein, The Netherlands

    J C Grutters & J M M van den Bosch

  3. Department of Clinical Chemistry, Sint Antonius Hospital, Nieuwegein, The Netherlands

    H J T Ruven

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  1. A Abdallah
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  2. H Sato
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Correspondence to K I Welsh.

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Abdallah, A., Sato, H., Grutters, J. et al. Inhibitor kappa B-alpha (IκB-α) promoter polymorphisms in UK and Dutch sarcoidosis. Genes Immun 4, 450–454 (2003). https://doi.org/10.1038/sj.gene.6364001

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