DR4 subtypes and their molecular properties in a population-based study of Swedish childhood diabetes.

Abstract	The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB10401 (62% patients and 25% controls; OR 4.95, p < 0.01) and 0404 (16% patients and 10% controls; OR 1.67, p < 0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB10302-DQA10301 (DQ8) (56% patients and 14% controls; OR 7.69, p < 0.01; 15% patients and 10% controls; OR 1.55, p < 0.05, respectively). When DRB10401 was linked to DQB10301-DQA10301 (DQ7) (6% patients and 11% controls; OR 0.52, p < 0.05), this DR4 subtypes was negatively associated with IDDM. Third, tests of strongest association allowed the following ranking of alleles or haplotypes DQB10302-DQA10301 (DQ8) > DQB10302 > DRB10401 > DRB10404 and the association of DRB1*0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA-DQ as a primary genetic risk factor for IDDM.
Authors	C B Sanjeevi, P Höök, M Landin-Olsson, I Kockum, G Dahlquist, T P Lybrand, A Lernmark
Journal	Tissue antigens (Tissue Antigens) Vol. 47 Issue 4 Pg. 275-83 (Apr 1996) ISSN: 0001-2815 [Print] England
PMID	8773316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References	HLA-DQ Antigens HLA-DR4 Antigen
Topics	Adolescent Base Sequence Child Child, Preschool Diabetes Mellitus, Type 1 (genetics) HLA-DQ Antigens (immunology) HLA-DR4 Antigen (chemistry, genetics) Humans Infant Infant, Newborn Molecular Sequence Data Molecular Structure Polymerase Chain Reaction Sweden

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