Journal
BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY
Volume 19, Issue 3, Pages 323-339Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.bpg.2005.01.001
Keywords
coeliac; genetic; linkage; genome scan; association; CTLA4; celiac
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Funding
- Wellcome Trust Funding Source: Medline
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Coeliac disease has a strong genetic component, higher than for many other common complex diseases. Possession of the HLA-DQ2 variant is required for presentation of disease causing dietary antigens to T cells, although this is also common in the healthy population. Non-HLA genetic factors account for the majority of heritable risk. Linkage studies have identified promising regions on chromosomes 5 and 19, with multiple other loci awaiting definitive confirmation in independent studies. Inherited variants in the tightly clustered chromosome 2q CD28-CTLA4-ICOS region are associated with disease, although of weak effect size. Larger sample sizes are necessary in coeliac disease genetic studies to detect small effects, alternatively meta-analysis offers promise. Newer methods including gene expression analysis and genome wide association studies will advance understanding of genetic susceptibility. Identification of coeliac disease genes may improve diagnostic/prognostic markers, basic understanding of disease aetiology, permit development of novel therapeutics and provide insight into other autoimmune disorders.
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