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Fine mapping of the CELIAC2 locus on chromosome 5q31-q33 in the Finnish and Hungarian populations.
Tissue Antigens 2009; 74(5):408-16TA

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.

Authors+Show Affiliations

Department of Medical Genetics and Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -