Alternative titles; symbols
DO: 10608;
Cytogenetic location: 3p21 Genomic coordinates (GRCh38) : 3:43,600,001-54,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p21 | {Celiac disease, susceptibility to, 9} | 612007 | 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 CELIAC9 is influenced by genetic variation in the chromosome 3p21 region, within a linkage disequilibrium (LD) block encompassing a cluster of chemokine receptor genes.
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 single-nucleotide polymorphism (SNP) rs6441961 (P overall = 3.14 x 10(-7)) maps within a large cluster of chemokine receptor genes on 3p21 that includes CCR1 (601159), CCR2 (601267), CCRL2 (608379), CCR3 (601268), CCR5 (601373), and XCR1 (600552). SNP rs6441961 lies 43 kb 3-prime to CCR3, the nearest gene.
In an Italian cohort involving 538 patients with celiac disease and 593 healthy controls, Romanos et al. (2009) found no association with the rs6441961 SNP previously reported by Hunt et al. (2008). The authors noted that this was the first celiac disease association study in a southern European cohort, and suggested that there may be population differences across Europe regarding the loci contributing to celiac disease.
In a study of 722 Spanish celiac patients and 794 ethnically matched controls, Dema et al. (2009) confirmed association with the 'A' risk allele of rs6441961 (OR, 1.32; p = 0.0004).
Dema, B., Martinez, A., Fernandez-Arquero, M., Maluenda, C., Polanco, I., de la Concha, E. G., Urcelay, E., Nunez, C. Association of IL18RAP and CCR3 with coeliac disease in the Spanish population. (Letter) J. Med. Genet. 46: 617-619, 2009. [PubMed: 19542083] [Full Text: https://doi.org/10.1136/jmg.2009.067041]
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]