Alternative titles; symbols
Cytogenetic location: 6q25.3 Genomic coordinates (GRCh38) : 6:155,200,001-160,600,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6q25.3 | {Celiac disease, susceptibility to, 12} | 612010 | 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.
The form of susceptibility to celiac disease here designated CELIAC12 is influenced by genetic variation in the 6q25.3 region, within a linkage disequilibrium (LD) block encompassing the TAGAP (609667) gene.
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. They identified single-nucleotide polymorphism (SNP) rs1738074 (P overall = 6.71 x 10(-8)) on chromosome 6q25.3 within a 200-kb LD block containing the TAGAP (609667) gene, itself within a larger region of weaker LD containing the RSPH3 gene (615876). TAGAP is expressed in activated T cells, has 3 isoforms, and is a Rho GTPase-activating protein important for modulating cytoskeletal changes.
Smyth et al. (2008) evaluated the association between type 1 diabetes (222100) and 8 loci related to the risk of celiac disease in 8,064 patients with type 1 diabetes, 2,828 families providing 3,064 parent-child trios, and 9,339 controls. The authors found significant association between IDDM21 (612521) and rs1738074 in the TAGAP gene, which is associated with CELIAC12.
In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) confirmed moderate association at rs1738074 (p = 0.0495).
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]
Smyth, D. J., Plagnol, V., Walker, N. M., Cooper, J. D., Downes, K., Yang, J. H. M., Howson, J. M. M., Stevens, H., McManus, R., Wijmenga, C., Heap, G. A., Dubois, P. C., Clayton, D. G., Hunt, K. A., van Heel, D. A., Todd, J. A. Shared and distinct genetic variants in type 1 diabetes and celiac disease. New Eng. J. Med. 359: 2767-2777, 2008. [PubMed: 19073967] [Full Text: https://doi.org/10.1056/NEJMoa0807917]
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]