Clinical genomicsCeliac Disease Genetics: Current Concepts and Practical Applications
Section snippets
Celiac Disease Is a Multifactorial Disorder With Complex Genetics
The celiac enteropathy develops as a result of an interplay between genetic and environmental factors (Figure 1). Gluten (consisting of the gliadin and glutenin subcomponents) is clearly a critical environmental component, and both HLA and non-HLA genes are thought to be predisposing genetic factors. The importance of genetic factors is illustrated by a high degree of familial clustering, with about 10% of first-degree relatives being affected,1 and by the high concordance rate (∼75%) among
Genetic Diagnostic Tests
The final diagnosis of celiac disease is based on the findings of typical histologic alterations of the small intestinal mucosa of patients eating gluten. A clinical response on a gluten exclusion diet is also considered to be of importance. Serologic tests, particularly measuring IgA antibodies to TG2, are very useful tools to predict the disease and to select patients for subsequent endoscopic examination. Recent recommendations also include HLA genotyping as a diagnostic adjunct.56 In this
Future Therapy and Disease Prevention
Many patients cope with the gluten-free diet easily. Others find that the dietary restrictions are laborious, negatively influencing their quality of life. Compliance with the gluten-free diet is often incomplete among celiac disease patients, and there is a need for alternative treatments. Encouragingly, the new insight into the molecular mechanisms of celiac disease has uncovered novel targets for therapy.60
The activation of the CD4 gluten-reactive T cells seems to be a critical checkpoint in
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2021, Digestive and Liver DiseaseCitation Excerpt :Amplified products were visualized on 2% agarose gels stained with 0.5 mg/mL ethidium bromide, using the E-Gel precast Agarose Electrophoresis System (Invitrogen Life Technologies, PA4 9RF Paisley, UK). HLA-DQ2 positive patients carried the HLA-DQ2.5 (encoded by the alleles DQA1*05 DQB1*0201) or the HLA-DQ2.2 (encoded by the alleles DQA1*0201 DQB1*0202) molecules, while HLA-DQ8 positive patients carried the HLA-DQ8 molecules (encoded by the alleles DQA1*03 DQB1*0302) [28]. DNA was extracted from snap-frozen duodenal mucosal samples by using commercial kits (Dneasy Blood&Tissue Kit, Qiagen, Hilden, Germany) following the manufacturer's instructions to assure an unbiased representation of the profiles of both Gram+ and Gram− bacteria [29].
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Supported by grants from the Research Council of Norway, the European Community (BHM4-CT98-3087, QLK1-CT-1999-00037, and QLK1-CT-2000-00657), the Norwegian Cancer Society, the Juvenile Diabetes Foundation International (3-2000-515 and 1-2004-793), the NIH (DK65965; together with C. Khosla), and EXTRA funds from the Norwegian Foundation for Health and Rehabilitation.