Alternative titles; symbols
DO: 10608;
Cytogenetic location: 1q31 Genomic coordinates (GRCh38) : 1:185,800,001-198,700,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q31 | {Celiac disease, susceptibility to, 7} | 612005 | 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 identify risk variants contributing to celiac disease susceptibility other than those in the HLA-DQ region (see CELIAC1, 212750), Hunt et al. (2008) genotyped 1,020 of the most strongly associated non-HLA markers identified by van Heel et al. (2007) in an additional 1,643 cases of celiac disease and 3,406 controls. The most significant single-nucleotide polymorphism (SNP) outside the HLA-DQ region and the previously identified IL2/IL21 region (see CELIAC6, 611598) was rs2816316 (P overall = 2.58 x 10(-11)) on 1q31, located within an approximately 70-kb linkage disequilibrium block containing the RGS1 gene (600323). The SNP rs2816316 maps 8 kb distal to the 5-prime end of RGS1. RGS family genes attenuate the signaling activity of G proteins by acting as GTPase-activating proteins. RGS1 regulates chemokine receptor signaling and is involved in B-cell activation proliferation. Rgs1-null mice have enhanced B-cell movement into and out of lymph nodes and heightened dendritic cell migratory response to chemokines. Hunt et al. (2008) found RGS1 expression in human small intestinal biopsies. Rgs1 is strongly expressed in murine intestinal intraepithelial lymphocytes, and Hunt et al. (2008) confirmed that T-cell Rgs1 expression seemed to be specific to the intestinal intraepithelial lymphocyte compartment and was not found in conventional splenic or thymic alpha-beta T cells. Intestinal epithelial lymphocytes have a key role in epithelial cell death and the development of villous atrophy in celiac disease.
In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) confirmed association at rs2816216 (p = 0.0123).
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]
Hunt, K. A., Zhernakova, A., Turner, G., Heap, G. A. R., Franke, L., Bruinenberg, M., Romanos, J., Dinesen, L. C., Ryan, A. W., Panesar, D., Gwilliam, R., Takeuchi, F., and 25 others. Newly identified genetic risk variants for celiac disease related to the immune response. Nature Genet. 40: 395-402, 2008. [PubMed: 18311140] [Full Text: https://doi.org/10.1038/ng.102]
Romanos, J., Barisani, D., Trynka, G., Zhernakova, A., Bardella, M. T., Wijmenga, C. Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease. J. Med. Genet. 46: 60-63, 2009. [PubMed: 18805825] [Full Text: https://doi.org/10.1136/jmg.2008.061457]
van Heel, D. A., Franke, L., Hunt, K. A., Gwilliam, R., Zhernakova, A., Inouye, M., Wapenaar, M. C., Barnardo, M. C. N. M., Bethel, G., Holmes, G. K. T., Feighery, C., Jewell, D., and 16 others. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nature Genet. 39: 827-829, 2007. [PubMed: 17558408] [Full Text: https://doi.org/10.1038/ng2058]