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Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

Genes & Immunity volume 6, pages 211–216 (2005)Cite this article

Abstract

Interleukin (IL)-18 is an important mediator of innate and adaptive immunity. We searched for an association of IL-18 promoter single-nucleotide polymorphisms (SNP) with rheumatoid arthritis (RA) in Caucasians. The entire study population was composed of two independent cohorts from Germany (n=200) and Scotland (n=410). Presence of IL-18 SNP at positions −607 and −137 was determined by allele-specific PCR in 327 RA patients and 283 healthy donors (HD). Diplotype distributions of both loci were in Hardy–Weinberg equilibrium (HWE) in the German and Scottish HD cohorts. In contrast, locus −607 was in HW disequilibrium in German, and locus −137 in Scottish RA patients. Diplotypic exact χ2 tests suggested that −607CC was overrepresented in German, and −137CC in Scottish RA patients, but conservative χ2 trend analyses could not prove any significant disease association of these single loci. SNP −607 and −137 were in strong linkage disequilibrium. The −607C*−137C haplotype was more prevalent in German RA (3.2 vs 1.2%) and in Scottish RA patients (4.1 vs 0.9%) than in the respective HD cohorts. These observations suggest that SNP of both positions contribute to the genetic background of RA pathogenesis.

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Acknowledgements

We are grateful to Dr J Arnemann, Institute for human genetics, University Hospital Frankfurt, Dr C Seidl, Red Cross blood donor service Baden-Wurttemberg Hessen, Frankfurt, Professor Dr JP Kaltwasser, Matthias Thun, Julia Bauer, and Ioana Lorenz, Centre for Rheumatic Diseases, Department of Internal Medicine, Frankfurt University Hospital for their engaged support of this project.

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Authors and Affiliations

  1. Centre for Rheumatic Diseases, University of Glasgow, Glasgow, Scotland, UK

    J A Gracie, J Murdoch, M Field, F McGarry, A Crilly, R Madhok & I B McInnes

  2. Medical Department III, JW Goethe-University, Frankfurt, Germany

    N Koyama & A Schobel

  3. Biometry and Population Genetics, Justus-Liebig-University, Giessen, Germany

    J Pons-Kühnemann

  4. Department of Rheumatology and Clinical Immunology/Allergology, Inselspital-University Hospital Berne, Switzerland

    B Möller

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  1. J A Gracie
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Correspondence to B Möller.

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Gracie, J., Koyama, N., Murdoch, J. et al. Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients. Genes Immun 6, 211–216 (2005). https://doi.org/10.1038/sj.gene.6364183

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