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Genetic association of coeliac disease susceptibility to polymorphisms in the ICOS gene on chromosome 2q33

Genes & Immunity volume 5, pages 85–92 (2004)Cite this article

Abstract

An interesting candidate gene region for coeliac disease (CD), a common multifactorial disease, is a segment on 2q33–37 harbouring the genes for the CD28, cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), inducible costimulator (ICOS), and programmed death-1 (PD-1), all receptors that regulate lymphocyte activation. Several studies have suggested a role for this locus in immune-mediated diseases. To study further our previous finding of genetic linkage of this region to CD, we studied 25 polymorphic markers to identify the putative disease-associated polymorphism. Transmission/disequilibrium test in 106 Finnish families with CD indicated that only four polymorphisms, all located in the ICOS gene, showed evidence for genetic association. Strong linkage disequilibrium (LD), based on the analysis of 424 haplotypes, encompassed not only the associated ICOS markers but also many polymorphisms in the CTLA4 gene. Our results demonstrate that due to LD, it appears not easy to identify the genuine susceptibility factor in this region without larger multipopulation studies. Furthermore, the results did not support the evidence that polymorphisms in CTLA4 were the major susceptibility locus for CD.

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Acknowledgements

We thank Drs Marta Alarcón-Riquelme and Ludmila Prokunina of Uppsala University, Uppsala, Sweden, for kind advice in the PD-1 typing. This study has been partially funded by the Commission of the European Communities, specific RTD programme ‘Quality of Life and Management of Living Resources’, QLRT-1999-00037, ‘Evaluation of the prevalence of the coeliac disease and its genetic components in the European population’. It does not necessarily reflect its views and in no way anticipates the Commission's future policy in this area. The study is also supported by the Sigrid Juselius Foundation, the Medical Research Fund of Finnish Red Cross Blood Transfusion Service, Maud Kuistila Memorial Foundation, the Medical Research Fund of Tampere University Hospital, Päivikki and Sakari Sohlberg Foundation and The Academy of Finland Research Council for Health, funding decision number 73489.

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  1. P Holopainen

    Present address: Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, Davos Platz, CH-7270, Switzerland

Authors and Affiliations

  1. Department of Tissue Typing and Research Laboratory, Division of Stem Cell and Transplantation Service, Finnish Red Cross Blood Service, Helsinki, Finland

    K Haimila, T Smedberg, J Partanen & P Holopainen

  2. Pediatric Research Centre, Medical School, Tampere University Hospital, Tampere, Finland

    K Mustalahti & M Mäki

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  1. K Haimila
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Correspondence to J Partanen.

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Haimila, K., Smedberg, T., Mustalahti, K. et al. Genetic association of coeliac disease susceptibility to polymorphisms in the ICOS gene on chromosome 2q33. Genes Immun 5, 85–92 (2004). https://doi.org/10.1038/sj.gene.6364040

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