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Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis

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Abstract

Introduction

Rheumatoid arthritis (RA) is a chronic inflammation disease that may involve extra-articular organs in addition to joints. Many proinflammatory cytokines are involved in the inflammatory process of RA. IκBα conjugates with NF-κB and is a key player in regulation of the inflammatory process. We carried out experiments to define the effect of different promoter polymorphisms on the transcriptional activities of IκBα promoter and the development of RA.

Methods

Different IκBα promoter reporters were constructed and were examined in human mononuclear cells, THP-1 cells. One hundred forty patients and 115 healthy controls were recruited from the Kaohsiung Medical University Hospital.

Results

The activities of IκBα promoter constructs with -826C, -550A, -519T, and -826T, -550A, -519T genotypes were expressed at one half the activity level of other constructs. Promoter constructs containing the sites -550A/T and -519T had a reduced risk of rheumatoid arthritis. The odds ratio of -826C/T genotype was significantly associated with an increase of risk in causing rheumatoid arthritis, whereas -826T/T genotype was associated only with a slightly increased risk of RA, but without statistical significance (odds ratio = 1.2; 95% confidence interval, 0.4–3.8).

Conclusion

The increase of T allele was associated with a significant increased risk and the tendency to the pathogenesis of RA. The association between IκBα promoter polymorphisms and disease severity of rheumatoid arthritis is partly due to different transcriptional activities of IκBα promoter and the activation of NF-κB.

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Acknowledgement

This study was supported by the grants from the National Science Council (NSC 94-2314-B-037-057, NSC 95-2314-B-037-007) and the Center of Excellence for Environmental Medicine, Kaohsiung Medical University.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ruei-Nian Li

  2. Graduate Institute of Medical College, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yu-Hung Hung & Chia-Hui Lin

  3. Faculty of Medicine, College of Medicine, Graduate Institute of Medical College, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yen-Hsu Chen & Jen-Hsien Yen

  4. Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jen-Hsien Yen

  5. Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jen-Hsien Yen

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  1. Ruei-Nian Li
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  2. Yu-Hung Hung
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  3. Chia-Hui Lin
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Correspondence to Jen-Hsien Yen.

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Li, RN., Hung, YH., Lin, CH. et al. Inhibitor IκBα Promoter Functional Polymorphisms in Patients with Rheumatoid Arthritis. J Clin Immunol 30, 676–680 (2010). https://doi.org/10.1007/s10875-010-9439-9

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  • DOI: https://doi.org/10.1007/s10875-010-9439-9

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