Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Susceptibility to celiac disease in Northern Europe is associated with the human leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended haplotype. The strong predominance of this haplotype within the Northern European celiac populations, together with the linkage disequilibrium which occurs between these loci, does not allow identification of the gene(s) primarily associated with disease susceptibility. Studies from Southern Europe using both serology and examination of restriction fragment length polymorphisms (RFLP) have demonstrated associations with DR3, DR7 and DQ2, suggesting that the DQ locus is primarily involved. We investigated 43 celiac patients and 41 healthy controls from Rome, Italy, using sequence-specific oligonucleotide (SSO) probes, in conjunction with gene amplification by the polymerase chain reaction (PCR), to determine alleles at the DRB, DQA1, DQB1 and DPB1 loci: 19% of celiac patients possessed the alleles DRB1*0301 DRB3*0101, 33% DRB1*0301 DRB3*0201 and 33% of celiac patients were heterozygous for DRB1*1101-1201/DRB1*0701. The strongest association with celiac disease susceptibility was the combination of alleles DQA1*0501 DQB1*0201 (91% celiac patients vs. 12% controls; p = 0.000002). There was no additional susceptibility associated with alleles at the DPB locus. This study confirms the hypothesis that susceptibility is associated with a particular combination of DQ alleles and the ethnic variation in DR frequencies is secondary to linkage disequilibrium with these DQ alleles.
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PMID:HLA class II alleles associated with celiac disease susceptibility in a southern European population. 135 80

The contribution of HLA-DP genes to celiac disease susceptibility has been investigated in 95 Italian patients, 41 with childhood and 54 with adult disease onset. Polymerase chain reaction amplification, sequence-specific oligonucleotide probe hybridization and restriction fragment length polymorphism analyses have been carried out. All celiac patients and 56 out of 128 random healthy controls were DQw2-positive. The frequency of the DPB1*0101 allele was significantly increased (pc = 0.002, relative risk 5.21) in patients with celiac disease (23.2%) compared to the whole panel of controls (5.5%), but not to the 56 controls bearing DQw2 (10.7%). No significant difference in the frequency of DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult (22.2%) onset. The DPB1*0101 allele was associated with both the DR3-DQw2 and DR7-DQw2 haplotypes. Moreover, our study has not confirmed the association with DPB1*0402 and DPB1*0301 previously reported in celiac children from southern Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation that the DP but not the DQ association appears to be ethnically dependent strongly support a secondary role of DP molecules in celiac disease susceptibility.
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PMID:HLA-DP polymorphism in northern Italian celiac patients. 136 87

Genotyping for HLA-DR, -DQ, and -DP antigens by restriction fragment length polymorphism (RFLP) analysis along with identification of restriction fragments associated with celiac disease (CD) were undertaken in 13 families in which more than one member had CD. Major histocompatibility complex class II haplotypes for the family members were constructed which included both genotypes and RFLP markers. In 12 of the families all the affected members shared an HLA haplotype which included HLA-DR3a, DQw2 and a BglII 4.0-kb DQA fragment. Eight of these 12 haplotypes also included HLA-DPw1 and both a RsaI 4.0-kb DPB fragment and an XbaI 16.0-kb DPA fragment. In one family, the two affected members shared an HLA-DR7, DQw2 haplotype, although both their second haplotypes included HLA-DR3a and -DQw2. The results suggest that HLA-DP genes do not play an independent predisposing role in the etiology of CD but do mark a disease-associated extended haplotype. This haplotype contains genes coding for specific HLA products which may be necessary for the disease to develop. The findings support the hypothesis that the presence of a specific DQ alpha/DQ beta heterodimer, encoded in a cis arrangement on HLA-DR3a haplotypes, predisposes to celiac disease.
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PMID:A family study confirms that the HLA-DP associations with celiac disease are the result of an extended HLA-DR3 haplotype. 167 3

Thirty-six coeliac children on gluten-containing diet were studied for AGA IgA and IgG levels. Patients were typed for HLA-A, -B, -C, -DR, -DQ antigens and data were analysed for any correlation between HLA-DR phenotype and AGA levels. AGA IgA and/or IgG were present in all these children. Subjects negative for DR3 or DR7 showed lower AGA levels than those DR3 + and/or DR7 positive. The data suggest that these patients could escape diagnosis if screening for those requiring intestinal biopsy is based only on AGA assay. The observation that coeliac children negative for DR3 and DR7 showed lower AGA levels is consistent with clinical and genetic heterogeneity of coeliac disease.
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PMID:HLA antigens and antigliadin antibodies in coeliac disease. 182 10

Regional variations in the human leucocyte antigen (HLA) distribution patterns of coeliac disease (CD) have been reported. This study focuses on phenotype frequencies of a cohort of Austrian paediatric CD patients in comparison with those recorded in the literature. HLA class I and II typing was performed in 136 CD patients and 667 healthy controls from the general population of the same geographical area. The HLA phenotypes of our controls agreed with those published for Caucasians. In our patients the relative risks (RR) were 6.43 for DR3 and 2.52 for DR7, the aetiologic fractions being 0.58 respectively 0.24. The highest RR (7.78) was found for DR3/DR7 heterozygotes. The RR for DR5 was increased in heterozygosities, either with DR3 (3.34) or DR7 (5.53), yet not for DR5 alone. Of our patients, 10% were lacking both DR3 and DR7 as well as B8, 82% of them were positive for DQw3. In these DR3 and DR7 negative patients, DR4 and DR5 were significantly more frequent than in the others. DR5 was also significantly more common in these patients compared to controls lacking the same antigens, whereas this did not hold true for DR4. Prospective studies are required to determine any link between these HLA heterogeneities and long-term progression of the disease.
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PMID:Human leucocyte class I and II antigens in coeliac disease: a study in an Austrian paediatric population. 191 80

We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus. The association with coeliac disease was further investigated. Msp I DP beta polymorphism was studied in 52 healthy subjects and 59 patients: a 4.9 kb fragment was present in 51% of patients with coeliac disease compared to 11.5% of control subjects (p less than 0.001). Furthermore, nearly all subjects with the DP alpha 3.5 kb fragment also had the DP beta 4.9 kb fragment. However, disease frequency was still increased in the DP alpha 3.5 positive/DP beta 4.9 negative group. In seven families, each with at least two affected members, while the DP alpha 3.5 fragment was frequently present in patients it did not preferentially segregate with any particular HLA haplotype--for example, those associated with DR3 or DR7--and therefore is not part of an extended haplotype associated with coeliac disease. We therefore conclude that a gene(s) in the HLA-DP region predisposes to coeliac disease independently of the HLA-DR/DQ regions.
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PMID:HLA-DP and coeliac disease: family and population studies. 197 34

The authors have studied the HLA genotypes in 17 Sicilian coeliac children, in their parents and in their healthy brothers. A positive association has been found between coeliac disease (C.D.) and HLA antigens; this was strongest firstly for DQW2 and than for DR7 and DR3. Those antigens however do not result specific for C.D., because they were present in healty-control population too and because one coeliac patient was DQW2, DR7 and DR3 negative. A distortion of vertical transmission of HLA haplotypes has been observed in the studied patients, and this occurred for DR3/DQW2 that was transmitted mainly by paternal way. Moreover, in the healty brothers of our coeliac subjects a significant reduction of HLA antigens DQW2, DR7 and DR3 has not been found. Those observation and the finding that in our families the responsible gene for C.D. seems to have a low penetrance, should induce to search others genetic markers for coeliac disease.
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PMID:[HLA and sprue: a study of Sicilian families with celiac disease]. 207 98

Patients with the late-onset form of celiac disease have been studied for HLA association by conventional serology (DR and DQ typing) and by oligonucleotide probing with gene amplification (DP typing). Patients and controls were sampled in the Bologna area of northern Italy. Almost all patients were positive for DQw2 (94%), being DR3 positive (72%) and/or DR7 positive (65%). The proportion of DR3/7 heterozygotes in the patients was significantly increased over that expected from the Hardy-Weinberg equilibrium. No positive association with DR5 and no significant increase of DR5/7 heterozygotes were observed. Among the DP alleles reported to exhibit an association with celiac disease in other populations, only DPB3 showed a moderate increase of a borderline significance, not attributable to a linkage disequilibrium with DQw2.
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PMID:Reassessment of HLA association with celiac disease in special reference to the DP association. 228 38

A population of 62 unrelated homogeneous Argentinian celiac pediatric patients were typed for HLA-A,B,C,DR, and DQ antigens. The association between celiac disease and the DR3 and DR7 antigens was confirmed. The specificity DQw2 was present in 95.2 per cent of the patients. Nevertheless, it was of interest that the most significant phenotypes observed were DR3/DR7, DR7/DR5, and DR3/DR5. The significance of these findings is discussed.
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PMID:HLA and celiac disease in Argentina: involvement of the DQ subregion. 231 51


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