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NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?

Genes & Immunity volume 5, pages 417–425 (2004)Cite this article

Abstract

NOD2/caspase recruitment domain (CARD)15 variants are identified in up to 50% of Crohn's disease (CD) patients. Functional variants of toll-like receptor-4 (TLR4) and CD14 genes may also be relevant to disease pathophysiology. We aimed to assess the contribution of NOD2/CARD15, TLR4 and CD14 variants in Scottish and Irish CD patients. In all, 612 patients with well-characterised inflammatory bowel disease (252 Scottish CD, 247 Scottish UC, 113 Irish CD) and 304 controls were genotyped for variants of NOD2/CARD15 (1007fsinsC, G908R, R702W, P268S), TLR4 (A299G) and CD14 (T-159C). Genotype–phenotype analyses were performed. Variant 1007fsinsC (P=0.003) and G908R (P=0.008) but not R702W (P=0.269) alleles were more prevalent in Scottish CD (4.7, 1.8 and 7.1%, respectively) than Scottish control (2.3, 0.3 and 5.4%). CD allelic frequencies were lower than the series from Europe (P<0.00001) and North America (P<0.00001) but not Scandinavia (P<0.7). Associations were identified with age at diagnosis (P=0.002), ileal disease (P<0.02), penetrating disease (P=0.04) and inflammatory joint disease (P<0.02). TLR4 and CD14 variants did not differ between CD and controls. In conclusion, we present compelling evidence for genetic heterogeneity within Europe. These NOD2/CARD15 variants have a minor contribution in Scottish and Irish CD patients, consistent with an emerging pattern from Northern Europe.

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Author notes

  1. I D R Arnott and E R Nimmo: These authors contributed equally to this work

Authors and Affiliations

  1. University Department of Medical Sciences, Gastrointestinal Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK

    I D R Arnott, E R Nimmo, H E Drummond, J Fennell, B R K Smith, E MacKinlay, J Morecroft, N Anderson & J Satsangi

  2. Dublin Molecular Medicine Centre and Department of Clinical, Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin, UK

    D Kelleher & R McManus

  3. Department of Clinical Medicine, Adelaide and Meath Incorporating the National Childrens Hospital, Tallaght, Dublin, UK

    M O'Sullivan

Authors
  1. I D R Arnott
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  2. E R Nimmo
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  3. H E Drummond
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  11. R McManus
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Correspondence to I D R Arnott.

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Arnott, I., Nimmo, E., Drummond, H. et al. NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe?. Genes Immun 5, 417–425 (2004). https://doi.org/10.1038/sj.gene.6364111

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  • DOI: https://doi.org/10.1038/sj.gene.6364111

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