An extended HLA-D region haplotype associated with celiac disease.

Howell, Mark D.; Smith, Jennifer; Austin, Raleigh K.; Kelleher, Dermot; Nepom, Gerald T.; Volk, B; Kagnoff, Martin F.

doi:10.1073/pnas.85.1.222

Cited by 53 publications

(27 citation statements)

References 29 publications

(28 reference statements)

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“…Several reports have recently indicated an association between CD and certain genomic DP polymorphisms (18,19). At present it is not clear whether both DQ and DP genes might contribute to susceptibility to CD or whether the DP associations are secondary to the DQ association.…”

Section: Resultsmentioning

confidence: 98%

Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.

Sollid

Markussen

et al. 1989

The Journal of Experimental Medicine

856

398

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Celiac disease (CD) is a malabsorptive disorder precipitated in genetically susceptible individuals by ingestion ofgluten . A significant part of the disease predisposition maps to the HLA class II region, but the primary HLA association is not known (1) . DR3 seems to be a susceptibility allele together with any other DR allele while DR7 is associated to CD almost only in combination with DR3 or DR5 (2, 3).The HLA-DR3DQw2 haplotype demonstrates the strongest association to CD (1-5) . We investigated whether DR3DQw2 negative patients might share parts of the genetic information ofthis HLA haplotype but encoded in trans position. When we compared amino acid sequences of different DQa and DQß chains we found that the DQa chain encoded by the DR3DQw2 haplotype is identical to that encoded by DR5DQw7 (6, 7), while the DQß chain of the DR3DQw2 haplotype is identical to that of DR7DQw2 except for a single amino acid difference in the second domain (8, 9; Lee, J. S., personal communication) . The pairing of a and ß chains seems to be determined by amino acid residues located in the first domains (10). Thus, individuals wao are DR5DQw7/DR7DQw2 heterozygous may by transcomplementation express the same (or almost the same) DQ a/0 heterodimers as those formed by DQAl and DQBI genes in cis position on the DR3DQw2 haplotype (see Fig . 1). As a first step to confirm this hypothesis we typed 94 CD children with synthetic DQA1 and DQB1 allele-specific oligonucleotide (ASO) probes. Here we report that all except one ofthese CD patients carry DQAI and DQB1 genes that may encode the same DQ a/ß heterodimer.

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Section: Resultsmentioning

confidence: 98%

Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.

Sollid

Markussen

et al. 1989

The Journal of Experimental Medicine

856

398

View full text Add to dashboard Cite

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“…It is conceivable that in the genetieally predisposed individual the onset ofthe disease may require some other genetie or environmental factors, such as an extended haplotype involving the DP locus (Howell et al, 1988;Bugawan e;Kagnoffe/a/., 1989;Colonnae/a/., 1990) and other hypothetical polymorphic loci (Weiss et al, 1983) or adenovirus infection (Kagnoff e;.…”

Section: Resultsmentioning

confidence: 99%

Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence

Mantovani

Corazza²,

Ángelini³

et al. 1991

Clinical and Experimental Immunology

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SUMMARYSusceptibility lo coeliac disease is strongly associated with some HLA class IF 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 ofthe HLA-DQ Al 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 ofthe HLA-DQ A gene using the restriction enzyme BglW 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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“…1. CD patients in the USA and England showed a very high incidence of certain alphaDP and betaDP chain alleles (Howell et al, 1988;Niven et aI., 1987); the most common allele in the USA was DPB I *030 I followed by DPB I *0402 and by DPB I *0 IO 1 (Kagnoff et al, 1989), while in a Caucasian English population an increase of DPB 1 *0 10 I was observed (Rosemberg et aI., 1989). The same RFLPs did not reveal any significant DP association in an Argentinian population (Herrera et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…, 1988). and DPB I alleles defined by restriction fragment length polymorphism (RFLP) analysis (Howell et al , 1988;Niven et aI. , 1987) or by probing polymerase chain reaction amplified genomic DNA, with sequence specific oligonucleotides (Bugawan et ai., 1989;Roep et al, 1988;Howell et aI., 1988;Niven et aI.…”

Section: Introductionmentioning

confidence: 99%

Distribution of HLA‐DPBl, ‐DQBI‐DQAl Alleles among Sardinian Celiac Patients

et al. 1994

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SUMMARYThe Sardinian population in many aspects differs from other Caucasoid populations, particularly for its degree of homogeneity. Forthis reason we have studied 50 adult Sardinian patients with celiac disease (CD) and 50 control healthy Sardinian individuals by RFLP analysis and by extensive oligotyping for 17 HLA-DPB I, 8-DQB I and 9-DQA I alleles, and established their -DPB I alleles and -DQB I -DQA I genotypes. The heterodimer HLA-DQB I *020 I I-DQA I *050 I, present in 96% of our patients, is strongly associated with CD susceptibility, confirming published reports. On the other hand we found in I I of 50 probands (22 %) the presence of the allele -DQB I *05021 DQAI*0102 . This genotype is extremely rare in other Caucasian populations and appears to confer limited protection in CD Sardinian patients.

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An extended HLA-D region haplotype associated with celiac disease.

Cited by 53 publications

References 29 publications

Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.

Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer.

Molecular analysis of HLA-DQ A alleles in coeliac disease lack of a unique disease-associated sequence

Distribution of HLA‐DPBl, ‐DQBI‐DQAl Alleles among Sardinian Celiac Patients

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