Alternative titles; symbols
DO: 10608;
Cytogenetic location: 5q31-q33 Genomic coordinates (GRCh38): 5:131,200,001-160,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q31-q33 | {Celiac disease, susceptibility to, 2} | 609754 | 2 |
Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002).
For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750.
To determine the localization of genetic risk factors for celiac disease in addition to 6p21.3 (212750), Greco et al. (1998) performed a systematic screening of the genome in 110 affected sib pairs and their parents. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of celiac disease. Replication of the regions of interest was then carried out on 71 pairs in which 1 sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci on 6p21.3, this study suggested that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiated the 2 forms. Using the maximum lod score method applied to a dense set of markers, Greco et al. (2001) analyzed 6 regions to which potential linkage of celiac disease had previously been proposed. In a new sample of 89 Italian sib pairs, they found evidence for linkage only for chromosome 5q. Their data from this study as well as the data from their previous report (Greco et al., 1998) were compatible with the presence of a risk factor for CD with a moderate effect, operating in addition to the well-known HLA risk factors.
Using pooled data from the European Genetics Cluster on Coeliac Disease, Babron et al. (2003) performed meta- and megaanalyses of genotype data from 2,025 individuals, 1,056 of whom had celiac disease. They confirmed the association to the HLA region, and also found a strong suggestion of a genetic risk factor in the 5q31-q33 region, with a maximum Zlr of 4.39, p = 6 x 10(-6). Linkage of celiac disease to this region had also been found by Naluai et al. (2001) and Liu et al. (2002).
Amundsen et al. (2007) performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families with celiac disease who demonstrated linkage to the 5q31-q33 region. They failed to identify an association signal of any of the markers that could account for the linkage signal in their cohort. They suggested that collective effects of multiple risk genes within the region, incomplete genetic coverage, or effects related to copy number are possible explanations for their findings.
Amundsen, S. S., Adamovic, S., Hellqvist, A., Nilsson, S., Gudjonsdottir, A. H., Ascher, H., Ek, J., Larsson, K., Wahlstrom, J., Lie, B. A., Sollid, L. M., Naluai, A. T. A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families. Europ. J. Hum. Genet. 15: 980-987, 2007. [PubMed: 17551518] [Full Text: https://doi.org/10.1038/sj.ejhg.5201870]
Babron, M.-C., Nilsson, S., Adamovic, S., Naluai, A. T., Wahlstrom, J., Ascher, H., Ciclitira, P. J., Sollid, L. M., Partanen, J., Greco, L., Clerget-Darpoux, F., European Genetics Cluster on Coeliac Disease. Meta and pooled analysis of European coeliac disease data. Europ. J. Hum. Genet. 11: 828-834, 2003. [PubMed: 14571266] [Full Text: https://doi.org/10.1038/sj.ejhg.5201051]
Farrell, R. J., Kelly, C. P. Celiac sprue. New Eng. J. Med. 346: 180-188, 2002. [PubMed: 11796853] [Full Text: https://doi.org/10.1056/NEJMra010852]
Greco, L., Babron, M. C., Corazza, G. R., Percopo, S., Sica, R., Clot, F., Fulchignoni-Lataud, M. C., Zavattari, P., Momigliano-Richiardi, P., Casari, G., Gasparini, P., Tosi, R., Mantovani, V., de Virgiliis, S., Iacono, G., D'Alfonso, A., Selinger-Leneman, H., Lemainque, A., Serre, J. L., Clerget-Darpoux, F. Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families. Ann. Hum. Genet. 65: 35-41, 2001. [PubMed: 11415521] [Full Text: https://doi.org/10.1046/j.1469-1809.2001.6510035.x]
Greco, L., Corazza, G., Babron, M.-C., Clot, F., Fulchignoni-Lataud, M.-C., Percopo, S., Zavattari, P., Bouguerra, F., Dib, C., Tosi, R., Troncone, R., Ventura, A., and 21 others. Genome search in celiac disease. Am. J. Hum. Genet. 62: 669-675, 1998. [PubMed: 9497251] [Full Text: https://doi.org/10.1086/301754]
Liu, J., Juo, S.-H., Holopainen, P., Terwilliger, J., Tong, X., Grunn, A., Brito, M., Green, P., Mustalahti, K., Maki, M., Gilliam, T. C., Partanen, J. Genomewide linkage analysis of celiac disease in Finnish families. Am. J. Hum. Genet. 70: 51-59, 2002. [PubMed: 11715113] [Full Text: https://doi.org/10.1086/338453]
Naluai, A. T., Nilsson, S., Gudjonsdottir, A. H., Louka, A. S., Ascher, H., Ek, J., Hallberg, B., Samuelsson, L., Kristiansson, B., Martinsson, T., Nerman, O., Sollid, L. M., Wahlstrom, J. Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11. Europ. J. Hum. Genet. 9: 938-944, 2001. [PubMed: 11840196] [Full Text: https://doi.org/10.1038/sj.ejhg.5200752]