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NRAMP1 (SLC11A1): A Plausible Candidate Gene for Systemic Sclerosis (SSc) with Interstitial Lung Involvement

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Abstract

Systemic sclerosis (SSc), also termed “scleroderma,” is a progressive, systemic disease of unknown origin characterized by excessive fibrosis, vascular abnormalities and immune dysfunction. Nramp 1 gene has multiple pleiotropic effects on macrophage activation pathways, including up-regulation of the chemokine/cytokine genes KC, tumor necrosis factor α, interleukin-1 b, inducible nitric oxide syntase, and major histocompatibility complex class II expression, as well as tumoricial activity and antimicrobial activity. All of these pleiotropic effects are important for resistance to infection, but they may also be involved in the induction and maintenance of autoimmune diseases. We analyzed four natural resistance associated macrophage protein 1 (NRAMP1) gene polymorphisms including 5′ promoter (GT)n microsatellite, INT4 (469 + 14G/C), 3′UTR (1729 + 55del4), and D543N (codon 543, Asp to Asn) in 52 systemic sclerosis patients with interstitial lung involvement and 136 healthy controls. We found a significant association between INT4, (GT)n polymorphisms (p = 0.006 and 0.027, respectively), and SSc. Our findings suggest that NRAMP1 is a plausible candidate gene for SSc.

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Acknowledgements

This work was supported by the Research Fund of Istanbul University, project numbers: BYP-9555/24032006.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Science Faculty, Istanbul University, 34118 Vezneciler, Istanbul, Turkey

    Ö. Ates & A. Topal-Sarıkaya

  2. Chest Disease Department, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

    B. Müsellim & G. Öngen

  3. Research and Application Center for Biotechnology and Genetic Engineering, Istanbul University, Istanbul, Turkey

    A. Topal-Sarıkaya

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  1. Ö. Ates
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  2. B. Müsellim
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  4. A. Topal-Sarıkaya
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Correspondence to Ö. Ates.

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Ates, Ö., Müsellim, B., Öngen, G. et al. NRAMP1 (SLC11A1): A Plausible Candidate Gene for Systemic Sclerosis (SSc) with Interstitial Lung Involvement. J Clin Immunol 28, 73–77 (2008). https://doi.org/10.1007/s10875-007-9134-7

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  • DOI: https://doi.org/10.1007/s10875-007-9134-7

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