Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1992-4-27
|
| pubmed:abstractText |
Insulin-dependent diabetes mellitus (IDDM) in whites is strongly associated with particular HLA-DQ alpha beta heterodimers composed of a DQ alpha chain with an arginine at residue 52 (Arg52+) combined to a DQ beta chain lacking an aspartic acid at residue 57 (Asp57-). With the aim of confirming this association, clarifying which heterodimers account for the highest risk of IDDM and explaining the excess risk of DR3-DQw2/DR4-DQw8, 115 unrelated white IDDM patients and 108 unrelated healthy nondiabetic control subjects were studied. With polymerase chain reaction and sequence-specific oligonucleotide probes, both patients and control subjects were typed for their HLA-DQA1 and DQB1 alleles and their DQA1-DQB1 haplotype and genotype frequencies were compared. Four major findings emerged from our analysis. 1) Arg52+ DQ alpha/Asp57- DQ beta heterodimers, formed in cis and/or in trans, are strongly associated with susceptibility to IDDM; 97% of patients and 46% of control subjects had at least one such susceptibility heterodimer (relative risk [RR] 32, confidence interval [Cl] 14.25-71.86, P less than 10(-7). 2) The degree of disease susceptibility depends on the number of such DQ heterodimers that a subject can express according to his or her DQA1-DQB1 genotype. The highest RR was observed in patients with four susceptibility DQ heterodimers (RR 41, Cl 17.05-95.9). 3) Only part of the susceptibility DQ heterodimers were significantly increased in patients, conferring IDDM susceptibility of different strength. The strongest association was with the DQA1*0501-DQB1*0302 combination formed in trans position (RR 35.2, CI 12.88-96.78, P less than 10(-7).(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-D Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-DQ Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotide Probes
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0012-1797
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
378-84
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1551498-Alleles,
pubmed-meshheading:1551498-Amino Acid Sequence,
pubmed-meshheading:1551498-Base Sequence,
pubmed-meshheading:1551498-Cell Line,
pubmed-meshheading:1551498-DNA,
pubmed-meshheading:1551498-Diabetes Mellitus, Type 1,
pubmed-meshheading:1551498-Disease Susceptibility,
pubmed-meshheading:1551498-Gene Frequency,
pubmed-meshheading:1551498-Genotype,
pubmed-meshheading:1551498-HLA-D Antigens,
pubmed-meshheading:1551498-HLA-DQ Antigens,
pubmed-meshheading:1551498-Haplotypes,
pubmed-meshheading:1551498-Histocompatibility Testing,
pubmed-meshheading:1551498-Humans,
pubmed-meshheading:1551498-Macromolecular Substances,
pubmed-meshheading:1551498-Molecular Sequence Data,
pubmed-meshheading:1551498-Oligodeoxyribonucleotides,
pubmed-meshheading:1551498-Oligonucleotide Probes,
pubmed-meshheading:1551498-Polymerase Chain Reaction,
pubmed-meshheading:1551498-Reference Values,
pubmed-meshheading:1551498-Risk Factors
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Dose effect of cis- and trans-encoded HLA-DQ alpha beta heterodimers in IDDM susceptibility.
|
| pubmed:affiliation |
Institut National de la Sante et de la Recherche Medicale (INSERM) U93, Saint Louis Hospital, Paris, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|