Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The susceptibility to develop celiac disease (CD) seems to be primarily associated to a particular HLA-DQ alpha/beta heterodimer encoded by the DQA1*0501 and DQB1*0201 alleles, in cis position on the DR3-DQ2 haplotype or in trans position by DR5-DQ7/DR7-DQ2 heterozygotes. However, exceptional patients exist who are neither DR3 nor DR5/DR7, particularly among Southern European populations. We therefore examined the DRB1, DQA1, and DQB1 alleles of 13 Spanish CD patients who were serologically typed to be neither DR3 nor DR5/DR7. Five patients were found to carry the DQA1*0501 and DQB1*0201 alleles either in cis or in trans position, three of them had previously been serologically mistyped. However, two of these patients carried DQA1*0501 and DQB1*0201 on haplotypes other than DR3 or DR5 in combination with DR7. One of the latter patients carried an unusual DR4-DQ2 haplotype, while another had an unusual DR8-DQ2 haplotype. Four of the remaining eight patients carried DR4-DQ8 haplotypes. Taken together, our findings provide further evidence that the DQ alpha/beta heterodimer encoded by the DQA1*0501 and the DQB1*0201 alleles confers the primary HLA-associated susceptibility to develop CD. However, our studies also corroborate that a second (and "weaker") HLA-associated CD susceptibility gene may be present on some DR4-carrying haplotypes.
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PMID:HLA-DR and -DQ genotypes of celiac disease patients serologically typed to be non-DR3 or non-DR5/7. 129 82

Restriction fragment length polymorphism analysis, using a single restriction enzyme TaqI-multiple-probe system for HLA-DRB1-DQB1 and -DQA1, was used to determine HLA-DR and -DQ frequencies in 56 unrelated celiac patients and 47 unrelated controls from the west of Ireland. In addition, HLA-DPB1 allelic frequencies were determined in the same group of patients and controls by using the technique of enzymatic DNA amplification of the polymorphic second exon of HLA-DPB1 genes in conjunction with sequence-specific oligonucleotide probing. The results suggest that HLA-DQ rather than HLA-DR is more important in conferring susceptibility to celiac disease. Furthermore, no association between HLA-DP and celiac disease was found in this study.
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PMID:HLA class II frequencies in celiac disease patients in the west of Ireland. 135 56

Susceptibility to coeliac disease is strongly associated with some HLA class II antigens, encoded by the HLA-D region. Since the HLA-DQ locus seems to be primarily involved, we have analysed by polymerase chain reaction amplification and allele-specific oligonucleotide hybridization the most polymorphic region of the HLA-DQ A1 gene. No difference was observed between the 20 coeliac patients and 20 HLA-D-matched healthy controls who took part in the study. Furthermore, in patients and controls, the restriction fragment length polymorphism analysis of the HLA-DQ A gene using the restriction enzyme BglII did not disclose any specific disease-associated fragment. Our results are not consistent with a unique DQ A coeliac disease-associated sequence, but rather with the hypothesis that some polymorphic residues or allelic hypervariable regions, although found also in the normal population, can predispose to coeliac disease due to their higher frequency in this condition.
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PMID:Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence. 167 Oct 7

Studies at the DNA and product level of B-cell lines of coeliac patients have shown a strong association between coeliac disease and the HLA-DQ alpha 2.3 and HLA-DQ beta 2.7 alleles. The monoclonal antisera SFR20-DQ alpha 5 and XIII-358.4, which specifically react with HLA-DQ alpha 2.3 and with HLA-DQ beta 2.3 and -DQ beta 2.7, respectively, have been used to detect the expression of these specificities in the small-intestinal mucosa of 7 coeliac patients and 11 non-coeliac persons. An immunoperoxidase technique on frozen tissue sections of jejunal biopsy specimens was used. Positive specimens showed immunoperoxidase staining of lymphocytes and histiocytes in the lamina propria. The epithelial cells showed no immunoperoxidase staining. Positive results at the intestinal level correlated with the HLA typing of the patients and controls. The distribution found for the HLA-DQ alleles in the intestinal mucosa makes the role of a HLA-DQ alpha/beta dimer as gliadin receptor at the epithelial cell less probable, but it is compatible with the hypothesis that these DQ molecules are involved in the regulation of the intestinal immune response to gluten.
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PMID:Expression of HLA-DQ antigens in the small-intestinal mucosa of patients with coeliac disease. 186 99

The finding that diseases such as type I diabetes, coeliac disease and multiple sclerosis are HLA-DQ associated is not easily explained by a simple hypothesis of DQ-restricted, autoreactive T cells, considering the generally marginal role of DQ in restricting responses. Consequently, there have been various attempts to find a differential role for DQ, from presentation of special antigens to preferential stimulation of suppressor cells. Here, Daniel Altmann and colleagues critically assess these proposals and put forward the alternative hypothesis that the effect of DQ on disease susceptibility may result from a special role in shaping the T-cell receptor repertoire.
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PMID:What is the basis for HLA-DQ associations with autoimmune disease? 191 Apr 48

The HLA-associated susceptibility to develop celiac disease may to a large extent be attributed to the combination of particular DQA1 and DQB1 genes, i.e., the DQA1*0501 and DBQB1*0201 alleles, located either in cis position (on the DR3DQw2 haplotype) or in trans position (DR5DQw7/DR7DQw2 heterozygous individuals). We report three alloreactive T lymphocyte clones that recognize an HLA-DQ alpha/beta heterodimer both when the DQA1*0501 and DQB1*0201 alleles are located in cis or in trans position. Thus, the celiac disease associated DQA1 and DQB1 genes encode a functionally expressed DQ alpha/beta heterodimer.
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PMID:T lymphocyte recognition of a celiac disease-associated cis- or trans-encoded HLA-DQ alpha/beta-heterodimer. 197 14

Coeliac disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities. Here we use a new DNA-based method of HLA-DP typing to analyse the distribution of DP beta alleles in a group of coeliac disease patients and healthy controls. Two specific DP beta alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DP beta sequences suggests that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DP beta alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQ alpha and beta alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DP beta allele are at increased risk for coeliac disease.
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PMID:A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease. 249 67

The HLA-DR3 haplotype is associated with increased risk of myasthenia gravis (MG) and a number of other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), coeliac disease, and premature ovarian failure (POF). With a cDNA probe for a DQ beta gene, a 15 kb Hinc II restriction fragment has been demonstrated in genomic DNA from 7 of 16 HLA-DR3 patients with MG, 1 of 19 healthy DR3 controls, and none of 24 DR3 patients with IDDM, coeliac disease, or POF. The HLA-DQ polymorphism may be closely linked to a genetic locus regulating immune responsiveness to acetylcholine receptor and susceptibility to MG.
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PMID:HLA-DQ beta-chain polymorphism linked to myasthenia gravis. 287 36

An HLA-DQ alpha cDNA probe showed upon hybridization a highly significant discrepancy between the RFLP of celiac disease patients and healthy controls. The 4.0-kb Bgl II restriction fragment was present in 97% of celiac disease patients (n = 30), compared to 56% in a healthy control population (n = 72) (RR = 14.9; p less than 0.0005). At the product level all celiac disease patients tested to date have one DQ alpha chain in common, designated HLA-DQ alpha 2.3, which is associated with the 4.0-kb Bgl II fragment. This HLA-DQ alpha allele identified at the DNA level and product level seems to be a better marker for genetic susceptibility to develop celiac disease than those available to date.
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PMID:An HLA-DQ alpha allele identified at DNA and protein level is strongly associated with celiac disease. 290 22

Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular combination of a DQA1 and a DQB1 gene. These genes are arranged in cis position on the DR3DQw2 haplotype and in trans position in DR5DQw7/DR7DQw2 heterozygous individuals. Thus, most CD patients may share the same cis- or trans-encoded HLA-DQ alpha/beta heterodimer.
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PMID:Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. 290 59


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