Linked Life Data

8971095

Source:http://linkedlifedata.com/resource/pubmed/id/8971095

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-1-24
pubmed:abstractText
Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease susceptibility is mainly conferred by DQ8 while DR4 subtypes confer different degrees of protection. Some DR4 subtypes (i.e., DRB1*0405, 0402, and 0401) confer little or no protection, while others (i.e., DRB1*0404, 0403, and 0406) cause an increasing degree of protection, possibly by binding a common protective peptide. Features of a protective peptide that fit such a model are briefly discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection.
pubmed:affiliation
Institute of Transplantation Immunology, The National Hospital, Oslo, Norway. d.e.undlien@rh.uio.no
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't