Celiac Disease Genetics: Current Concepts and Practical Applications

Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
Clinical Gastroenterology and Hepatology (Impact Factor: 7.9). 10/2005; 3(9):843-51. DOI: 10.1016/S1542-3565(05)00532-X
Source: PubMed


Celiac disease is a multifactorial disease with complex genetics. Both HLA and non-HLA genes contribute to the genetic component, but recent findings suggest that the importance of non-HLA genes might have been overestimated. No susceptibility genes other than HLA-DQ have yet been identified in celiac disease. In contrast to the meager knowledge regarding non-HLA genes, we have acquired a detailed understanding about which HLA genes are predisposing for disease, and how they are involved in the pathogenesis. This knowledge might pave the road for novel treatments for the disease. The role of HLA as a necessary, but not sufficient, genetic factor can moreover be used for diagnostic purposes to exclude a celiac disease diagnosis. The applicability of HLA genotyping is particularly useful for excluding celiac disease in family members or risk groups with fairly unbiased distribution of HLA alleles (ie, patients with Turner syndrome and patients with Down syndrome) and in patients with a clinical suspicion of celiac disease.

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    • "The signature of HLA class ii genes in 2003) The true prevalence of CD is difficult to estimate because of the variable presentation of the disease, particularly since many patients can have little or no symptoms. A significant proportion of the genetic predisposition comes from MHC-linked genes, estimated to account for about 50% of the genetic load (Sollid and Lie, 2005). CD appears to represent a spectrum of clinical features and presentations classified as follows:. "
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    ABSTRACT: The objective of this study was to investigate the association of HLA Class frequencies in Sudanese patients with celiac disease. All blood specimens from celiac disease patients (n=70), and and ELISA. All tests were repeated on all patients (n=70) to check their response to the Gluten free diet (GFD). HLA the gel was done by using One Lambda Software. Analysis of case the Chi in 74.3 % of the patients compared to 4.4. The frequency of HLA and in healthy controls respectively (p=0.006) with a risk factor of 3.8. HLA DQ7) was controls (p= 0.011) with a relative risk of 9.3. This in contrast to Caucasian patients where the frequency of HLA patients and controls regarding HLA 17.14% patients compared to 30% in the controls (p=0.18) with a relative risk of 0.48. HLA highly specific to Sudanese CD compared to HLA
    No preview · Article · May 2015 · International Journal of Current Research
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    • "Upon initial interpretation of biopsy results, celiac disease was felt to be a possibility, but since total IgA and IgG were low, negative celiac serologic testing proved difficult to interpret. Genetic testing revealed that he was negative for HLA DQ2 and DQ8 markers, so celiac disease was felt to be unlikely since these haplotypes are typically present in individuals with celiac disease [6]. With no evidence for infection, the possibility of MMF-related enterocolitis was felt to be the most likely explanation for his symptoms. "
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    ABSTRACT: Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as "MMF-related enterocolitis," has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients. In previously reported cases, symptoms and abnormal histopathology improve with dose reduction of MMF. We describe a series of three pediatric patients with varied underlying disease process who presented with severe diarrhea and histopathologic findings characteristic of MMF-related enterocolitis, who share a novel finding of weight loss as a complication of MMF-related enterocolitis in pediatric patients.
    Full-text · Article · Oct 2012
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    • "CD is a multifactorial disorder including both genetic and environmental factors whose relative weight is not yet fully understood. Differences in concordance rates in monozygotic (86%) and dizygotic (20%) twins strongly suggest a relevant influence of genetic factors, of which HLA (Human Leukocyte Antigen) is estimated to contribute for 40–50% to disease development [3, 4]. In particular, while roughly 95% of CD patients carries HLA-DQ2 (DQA1*0501/DQB1*0201), most individuals that are not HLA-DQ2 positive express HLA-DQ8 (DQA1*0301/DQB1*0302). "
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    ABSTRACT: In the present paper, the controversial hypothesis suggesting ancient grains might show lower immunogenic properties and therefore the possibility to introduce them in the diet of wheat-sensitive people, including celiac patients, was investigated. The immunogenic potential of the ancient durum wheats Graziella Ra and Kamut was studied by comparison to the durum accessions Cappelli, Flaminio, Grazia and Svevo. Experiments were carried out with two monoclonal antibodies (mAbs) raised against α-gliadin peptides p31-49 and p56-75 (the latter containing the overlapping DQ2-Glia-α1 and DQ2-Glia-α2 epitopes), toxic for celiac patients. For all accessions, a few α-gliadin alleles were also cloned, sequenced and translated into aminoacid sequences. Several aminoacid substitutions or deletions were detected in p31-49, DQ2-Glia-α1 and DQ2-Glia-α2 epitopes, nevertheless, ELISA constantly showed antibody-antigen positive reactions which led us to suggest that mAbs binding was not apparently affected by polymorphisms. Moreover, a few substitutions were also observed in DQ2-Glia-α3 and DQ8-Glia-α1 epitopes. Although some DQ2-Glia-α1 and DQ2-Glia-α2 variants evidenced herein were previously reported to have a diminished or abolished T cell stimulatory capacity, present results cannot confirm that ancient durum wheats would be less CD-toxic. In conclusion, we strongly advice celiac patients from consuming ancient wheats including Graziella Ra or Kamut.
    Full-text · Article · May 2012 · The Scientific World Journal
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