Tags

Type your tag names separated by a space and hit enter

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

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

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

    , , , , , , , , , ,

    Source

    Tissue antigens 74:5 2009 Nov pg 408-16

    MeSH

    Case-Control Studies
    Celiac Disease
    Chromosome Mapping
    Chromosomes, Human, Pair 5
    Family
    Finland
    Gene Frequency
    Genetic Linkage
    Genetic Loci
    Genetics, Population
    Humans
    Hungary
    Polymorphism, Single Nucleotide

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19845895

    Citation

    Koskinen, L L E., et al. "Fine Mapping of the CELIAC2 Locus On Chromosome 5q31-q33 in the Finnish and Hungarian Populations." Tissue Antigens, vol. 74, no. 5, 2009, pp. 408-16.
    Koskinen LL, Einarsdottir E, Korponay-Szabo IR, et al. Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations. Tissue Antigens. 2009;74(5):408-16.
    Koskinen, L. L., Einarsdottir, E., Korponay-Szabo, I. R., Kurppa, K., Kaukinen, K., Sistonen, P., ... Saavalainen, P. (2009). Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations. Tissue Antigens, 74(5), pp. 408-16. doi:10.1111/j.1399-0039.2009.01359.x.
    Koskinen LL, et al. Fine Mapping of the CELIAC2 Locus On Chromosome 5q31-q33 in the Finnish and Hungarian Populations. Tissue Antigens. 2009;74(5):408-16. PubMed PMID: 19845895.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations. AU - Koskinen,L L E, AU - Einarsdottir,E, AU - Korponay-Szabo,I R, AU - Kurppa,K, AU - Kaukinen,K, AU - Sistonen,P, AU - Pocsai,Z, AU - Széles,G, AU - Adány,R, AU - Mäki,M, AU - Kere,J, AU - Saavalainen,P, PY - 2009/10/23/entrez PY - 2009/10/23/pubmed PY - 2010/2/2/medline SP - 408 EP - 16 JF - Tissue antigens JO - Tissue Antigens VL - 74 IS - 5 N2 - 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. SN - 1399-0039 UR - https://www.unboundmedicine.com/medline/citation/19845895/Fine_mapping_of_the_CELIAC2_locus_on_chromosome_5q31_q33_in_the_Finnish_and_Hungarian_populations_ L2 - https://doi.org/10.1111/j.1399-0039.2009.01359.x DB - PRIME DP - Unbound Medicine ER -