title: HLA heterozygosity in insulin-dependent diabetes is most frequent at the DQ locus.
abstract: Restriction fragment length polymorphism using an HLA-DQ beta-chain genomic probe showed that 63 children with insulin-dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA-DR3 and/or 4 and 75% (47/63) for HLA-B8 and/or 15. The 36 (56%) DR3-positive children were all 4-kb-positive; however, a total of 44 (70%) children were 4-kb-positive (P less than 0.02). The 55 (87%) DR4-positive children were all 12-kb-positive, but a total of 56 (89%) were 12-kb-positive (NS). The heterozygosity at the HLA region increased from 11/63 (18%) for HLA-B8/15 to 29/63 (46%) for HLA-DR3/4 (P less than 0.0004) and to 37/63 (59%) for the HLA-DQ 4 kb/12 kb fragments (P less than 0.02). The test of an equal probability of a positive result under the adjacent pair of tests indicates that the increased risk of developing IDDM in association with HLA-DQ is to a great extent due to heterozygosity at this locus. There were no differences between the 4 kb/12 kb and the DR3/4-positive IDDM children with respect to fasting or meal-stimulated C peptide, insulin requirement, or levels of insulin antibodies formed during the first 12 months of insulin therapy. Our results support the hypothesis that HLA-DQ is closely associated with an increased risk of childhood IDDM, and when typed for at this locus parameters of the clinical course were homogeneous, suggesting that factors other than HLA-DQ may determine previously observed differences between IDDM children in clinical or functional parameters.
authors.affiliation: Hagedorn Research Laboratory, Gentofte, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Michelsen
authors.forename: R
authors.initials: R
authors.lastname: Wassmuth
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
authors.forename: L
authors.initials: L
authors.lastname: Fisher
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011110:Polymorphism, Genetic
chemical_list: D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens