Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations

Authors

  • L. L. E. Koskinen,

    1. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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  • E. Einarsdottir,

    1. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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  • I. R. Korponay-Szabo,

    1. Coeliac Disease Center, Heim Pal Children's Hospital, Budapest, Hungary
    2. Department of Pediatrics, University of Debrecen, Medical Health and Science Center, Debrecen, Hungary
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  • K. Kurppa,

    1. Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland
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  • K. Kaukinen,

    1. Medical School, University of Tampere and Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
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  • P. Sistonen,

    1. Finnish Red Cross Blood Service, Helsinki, Finland
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  • Z. Pocsai,

    1. Faculty of Public Health, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary
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  • G. Széles,

    1. Faculty of Public Health, Department of Epidemiology and Biostatistics, University of Debrecen, Debrecen, Hungary
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  • R. Ádány,

    1. Faculty of Public Health, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary
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  • M. Mäki,

    1. Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital, University of Tampere, Tampere, Finland
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  • J. Kere,

    1. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    2. Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden
    3. Folkhälsan Institute of Genetics, Helsinki, Finland
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  • P. Saavalainen

    Corresponding author
    1. Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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Päivi Saavalainen
Department of Medical Genetics
Haartman Institute Biomedicum Helsinki
PO Box 63
FIN-00014 University of Helsinki
Finland
Tel: +358 9 1912 5086
Fax: +358 9 1912 5624
e-mail: paivi.saavalainen@helsinki.fi

Abstract

Celiac disease is a chronic inflammation of the small intestine, arising in genetically predisposed individuals as a result of ingestion of dietary gluten. The only confirmed and functionally characterised genetic risk factors for celiac disease are the DQ2 or DQ8 heterodimers at the major histocompatibility complex (MHC) class II locus (CELIAC1). These genes are necessary but alone not sufficient for disease onset. Genome-wide linkage scans have suggested chromosome 5q31-q33 (CELIAC2) as an important risk locus for celiac disease. This region has also been associated to other inflammatory disorders, although as yet, no clear gene associations have been found. In the current study, 11 celiac disease candidate loci were screened for genetic linkage in the Hungarian population. As the CELIAC2 locus showed the strongest evidence for linkage, this locus was selected for follow-up. Seventeen candidate genes were selected from the CELIAC2 locus, and genotyped using 48 haplotype tagging single nucleotide polymorphisms (SNPs) in large Finnish and Hungarian family materials. A subset of these, 40 tagging SNPs in 15 genes, were genotyped in an independent set of Finnish and Hungarian cases and controls. We confirmed linkage of this region with celiac disease and report strong linkage in both the Finnish and Hungarian populations. The association analysis showed modest associations throughout the whole region. These association findings were not replicated in the case–control datasets. Our study strongly supports the role of the CELIAC2 locus in celiac disease, but it also highlights the need for a more powerful study design in the region, to locate the true disease risk variants.

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