Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q33.2 | {Celiac disease, susceptibility to, 3} | 609755 | 3 | CTLA4 | 123890 |
A number sign (#) is used with this entry because of evidence that susceptibility to celiac disease-3 (CELIAC3) is conferred by polymorphism in the CTLA4 gene (123890) on chromosome 2q33.
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 phenotypic information and a discussion of genetic heterogeneity of celiac disease, see 212750.
Using a candidate gene approach, Djilali-Saiah et al. (1998) identified a polymorphism in the cytotoxic T lymphocyte-associated-4 (CTLA4) gene as a putative non-HLA predisposition locus in patients with celiac disease. An A-to-G substitution at position 49 (A49G) in exon 1 of the CTLA4 gene corresponds to a threonine-to-alanine amino acid change in the expressed protein (123890.0001). The A allele was found by Djilali-Saiah et al. (1998) to be significantly overrepresented in 101 patients with celiac disease compared with 130 controls (82.2% vs 65.8%, p less than 0.0001), reflecting an increased frequency of A/A homozygotes among patients as compared with controls (68.3% vs 47.7%, p = 0.002). This effect was maintained even after stratifying the patients according to their HLA class II genotype (see 146880), suggesting an HLA-independent disease susceptibility.
Naluai et al. (2000) analyzed the 49A/G polymorphism in 107 Swedish and Norwegian families with celiac disease and found a significant association with preferential transmission of the 49A allele by the transmission disequilibrium test (p less than 0.007). Nonparametric linkage analysis yielded a score of 2.1 (p = 0.018), suggesting that the CTLA4 region is a susceptibility region in celiac disease.
Van Belzen et al. (2004) genotyped 215 Dutch patients with celiac disease and 213 controls for the 49A-G (123890.0001) and CT60 (123890.0002) polymorphisms in the CTLA4 gene. They found no significant difference between patients and controls in the frequency of the 49G allele, but did find an increase in the frequency of the CT60 G allele in patients (p = 0.048).
Djilali-Saiah, I., Schmitz, J., Harfouch-Hammoud, E., Mougenot, J.-F., Bach, J.-F., Caillat-Zucman, S. CTLA-4 gene polymorphism is associated with predisposition to coeliac disease. Gut 43: 187-189, 1998. [PubMed: 10189842] [Full Text: https://doi.org/10.1136/gut.43.2.187]
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]
Naluai, A. T., Nilsson, S., Samuelsson, L., Gudjonsdottir, A. H., Ascher, H., Ek, J., Hallberg, B., Kristiansson, B., Martinsson, T., Nerman, O., Sollid, L. M., Wahlstrom, J. The CTLA4/CD28 gene region on chromosome 2q33 confers susceptibility to celiac disease in a way possibly distinct from that of type 1 diabetes and other chronic inflammatory diseases. Tissue Antigens 56: 350-355, 2000. [PubMed: 11098935] [Full Text: https://doi.org/10.1034/j.1399-0039.2000.560407.x]
van Belzen, M. J., Mulder, C. J. J., Zhernakova, A., Pearson, P. L., Houwen, R. H. J., Wijmenga, C. CTLA4 +49A/G and CT60 polymorphisms in Dutch coeliac disease patients. Europ. J. Hum. Genet. 12: 782-785, 2004. [PubMed: 15199380] [Full Text: https://doi.org/10.1038/sj.ejhg.5201165]