HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis

Sollid, Ludvig M.; Thorsby, E.

doi:10.1016/0016-5085(93)90912-v

Cited by 553 publications

(339 citation statements)

References 74 publications

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“…Therefore, individuals with celiac disease almost always have the DQ2 or DQ8 molecule, such that the absence of either of these molecules by genetic testing virtually excludes the possibility of celiac disease. On the other hand, the presence of either molecule does not guarantee that an individual will develop celiac disease, since DQ2 is present in approximately 30% of the general population, and either DQ2 or DQ8 is present in 40% of the general population (41,42), whereas only about 3% of the general population having DQ2 will develop celiac autoimmunity (43). There is not a large role for genetic testing in celiac disease.…”

Section: Diagnosis (376) (Figure 2a and 2b)mentioning

confidence: 99%

Celiac Disease: Pathophysiology, Clinical Manifestations, and Associated Autoimmune Conditions

Barker

Liu

2008

Advances in Pediatrics

161

133

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Section: Diagnosis (376) (Figure 2a and 2b)mentioning

confidence: 99%

Celiac Disease: Pathophysiology, Clinical Manifestations, and Associated Autoimmune Conditions

Barker

Liu

2008

Advances in Pediatrics

161

133

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“…4,5 The genetic susceptibility to CD is confirmed by its high familial incidence (about 10% of first degree relatives of celiac patients are affected by the disease) and by its strict linkage with some human leukocyte antigen (HLA) class 2 alleles (up to 95% celiacs are HLA-DQ2 positive with the typical heterodimer DQA1*0501/DQB1*0201, whereas the remaining 5% are HLA-DQ8 positive HLA-DQB1*0302). 6,7 Because about 20-30% of healthy people in Western countries display the same HLA pattern, the presence of HLA-DQ2 and/or HLA-DQ8 must be considered an indispensable prerequisite for the disease but cannot alone justify the development of CD. Therefore, non-HLA genetic factors are likely to be required for the development of disease.…”

Section: Introductionmentioning

confidence: 99%

Celiac disease: diagnostic criteria in progress

2011

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Until a few years ago, celiac disease (CD) was thought to be a rare food intolerance that was confined to childhood and characterized by severe malabsorption and flat intestinal mucosa. Currently, CD is regarded as an autoimmune disorder that is common in the general population (affecting 1 in 100 individuals), with possible onset at any age and with many possible presentations. The identification of CD is challenging because it can begin not only with diarrhea and weight loss but also with atypical gastrointestinal (constipation and recurrent abdominal pain) and extra-intestinal symptoms (anemia, raised transaminases, osteoporosis, recurrent miscarriages, aphthous stomatitis and associated autoimmune disorders), or it could be completely symptomless. Over the last 20 years, the diagnostic accuracy of serology for CD has progressively increased with the development of highly reliable tests, such as the detection of IgA tissue transglutaminase and antiendomysial and IgG antideamidated gliadin peptide antibodies. The routine use of antibody markers has allowed researchers to discover a very high number of 'borderline' cases, characterized by positive serology and mild intestinal lesions or normal small intestine architecture, which can be classified as potential CD. Therefore, it is evident that the 'old celiac disease' with flat mucosa is only a part of the spectrum of CD. It is possible that serology could identify CD in its early stages, before the appearance of severe intestinal damage. In cases with a positive serology but with mild or absent intestinal lesions, the detection of HLA-DQ2 and HLA-DQ8 can help reinforce or exclude the diagnosis of gluten sensitivity.

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“…It has been well established that the primary association is with HLA-DQ2, with over 90% of patients expressing this molecule. 6 There is substantial evidence for involvement of DQ2 in coeliac disease pathogenesis. Gluten-derived peptides are modified by the enzyme tissue transglutaminase, which improves binding to DQ2 on the surface of antigen-presenting cells.…”

Section: Introductionmentioning

confidence: 99%

“…In North European populations, the DQA1*05 and DQB1*02 alleles are frequently present on the extended HLA-B8-DR3-DQ2 haplotype. 6,9 This haplotype has also been shown to be associated with other autoimmune disorders, including type I diabetes mellitus, systemic lupus erythematosus, Graves' disease, Hashimoto's disease and myasthenia gravis, suggesting that the genes on this haplotype are involved in autoimmunity in general (for a review, see Candore et al 10 ). In coeliac disease, it was shown that different DQ2 genotypes account for different disease risks.…”

Section: Introductionmentioning

confidence: 99%

Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients

et al. 2004

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The major genetic susceptibility to coeliac disease is contributed by the human leukocyte antigen (HLA) region. The primary association is with the HLA-DQ2 molecule, encoded by the DQA1*05 and DQB1*02 alleles, which is expressed by over 90% of patients. The aim of our study was to perform an extensive scan of the entire HLA region to determine whether there is evidence for the presence of additional HLA susceptibility genes for coeliac disease in the Dutch population, acting independently of DQ2. In all, 16 microsatellite markers and the DQA1 and DQB1 genes were genotyped in simplex cis DQ2-positive coeliac disease families and cis DQ2-positive control families. Allele frequencies of markers on phase-known DQ2-positive haplotypes transmitted to patients were compared to a combined group of DQ2-positive nontransmitted and control haplotypes, thereby controlling for the DQ2 contribution. No significant differences at any of the marker loci were detected, suggesting that DQ2 is the major HLA risk factor for coeliac disease. Individuals homozygous for DQ2 or heterozygous for DQA1*05-DQB1*02/DQA1*0201-DQB1*02 were found to be at five-fold increased risk for development of coeliac disease (Po10 À8 ). This risk seems to be conferred by the presence of a second DQB1*02 allele next to one DQA1*05-DQB1*02 haplotype, independently of the second DQA1 allele.

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HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis

Cited by 553 publications

References 74 publications

Celiac Disease: Pathophysiology, Clinical Manifestations, and Associated Autoimmune Conditions

Celiac Disease: Pathophysiology, Clinical Manifestations, and Associated Autoimmune Conditions

Celiac disease: diagnostic criteria in progress

Defining the contribution of the HLA region to cis DQ2-positive coeliac disease patients

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