Journal
TISSUE ANTIGENS
Volume 78, Issue 6, Pages 428-437Publisher
WILEY
DOI: 10.1111/j.1399-0039.2011.01791.x
Keywords
celiac; Finnish; Hungarian; Immunochip; linkage; susceptibility
Categories
Funding
- EU Commission [MEXT-CT-2005-025270]
- Academy of Finland
- Hungarian Scientific Research Fund [OTKA 61868]
- University of Helsinki
- Tampere University Hospital
- Pirkanmaa Hospital District
- Yrjo Jahnsson Foundation
- Foundation of Pediatric Research
- Sigrid Juselius Foundation
- Finnish Cultural Foundation
- Maud Kuistila Memorial Foundation
- Finnish Society for Gastroenterological Research
- Finnish Celiac Disease Society
- Uppsala University, Uppsala University Hospital, Science for Life Laboratory - Uppsala
- Swedish Research Council [80576801, 70374401]
Ask authors/readers for more resources
Coeliac disease is a chronic inflammatory condition of the small intestine, triggered by dietary exposure to gluten in genetically susceptible individuals. Risk alleles at HLA-DQA1 and HLA-DQB1 are necessary for disease development, but are alone not sufficient for disease onset. We aimed to identify novel loci underlying susceptibility to coeliac disease through the use of extended Finnish and Hungarian families with multiple affected individuals. An initial whole-genome linkage approach yielded several loci that were followed up further using the Immunochip custom array. Loci with a parametric logarithm of odds (LOD) score of >1.3 were identified at 4q, 6p [human leukocyte antigen (HLA) region], 6q, 7p, 17p, 17q and at 22p. The 4q and 6q loci have been identified previously in coeliac disease risk, whereas follow-up analyses indicate that the 17p and 22p loci may be novel risk loci for coeliac disease. These loci harbour previously described risk variants for other autoimmune diseases, but their segregation patterns do not explain the linkage to coeliac disease. We followed up the linkage to the 4q region, containing the previously described interleukin (IL)2 and IL21 genes. The risk variants at 4q in the studied pedigrees are most likely distinct from previously described risk variants, indicating that the observed linkage may be due to rare high-risk variants of still unknown nature. The importance of this locus to coeliac disease risk was further shown by the finding that serum levels of IL21 were elevated in both untreated and treated coeliac patients compared to controls.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available