title: ICA+ relatives with DQA1*0102/DQB1*0602 have expected 0602 sequence and DR types.
abstract: The HLA haplotype DQA1*0102/DQB1*0602 reportely confers protection from type 1 diabetes. DQA1*0102/DQB1*0602 is present in more than 7% of ICA positive relatives screened as part of the Diabetes Prevention Trial--type 1. The presence of autoantibodies in these subjects suggests that the mechanism that protects DQB1*0602 subjects from diabetes occurs after the disease process has been initiated. However, as previously suggested, the method used to type the DQB1*0602 alleles may have lacked the sensitivity to identify alleles similar, but not identical, to DQB1*0602. In addition unusual extended haplotypes may be presented that could help account for the presence of diabetes autoantibodies. We therefore sequenced and performed extended haplotyping on samples from ICA+ relatives with DQA1*0102/DQB1*0602. In this group, sequencing confirmed DQB1*0602 in 149/150, and 152/165 have the common DRB1*1501-DQB1*0602 haplotype. Thus, high resolution typing of class II alleles either by PCR-based oligotyping or nucleotide sequencing fail to indicate any unusual genetic characteristics about these antibody-positive relatives, of which few are expected to progress to clinical disease.
authors.affiliation: Benaroya Research Institute at Virginia Mason Research Center, Seattle, WA 98101, USA. cjgreen@vmresearch.org
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Lakshmi K
authors.initials: LK
authors.lastname: Gaur
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D005500:Follow-Up Studies; D005802:Genes, MHC Class II / Q000235:genetics; D005820:Genetic Testing; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; C024211:islet cell antibody