title: Effects of the second HLA-DQ haplotype on the association with childhood insulin-dependent diabetes mellitus.
abstract: Analysis of HLA-DQ molecules in a large study comprising 425 consecutively diagnosed Swedish Caucasians with IDDM and 367 age, sex and geographically matched controls confirms previous observations that: (a) DQB1*0302-DQA1*0301 confer susceptibility in a dominant manner, except when they are associated with DQB1*0602-DQA1*0102; (b) DQB1*0501-DQA1*0201 does not confer susceptibility to IDDM in either homozygous or heterozygous combinations with any other DQ molecules except when it is in association with DQB1*0302-DQA1*0301; (c) heterozygous combinations of DQB1*0302-DQA1*0301 and DQB1*0501-DQA1*0201 confer the highest risk to IDDM; (d) in DQ2 positive patients being negative for DQ8 in second haplotype (n = 58) the susceptibility may be explained by DR, since all these patients were DR3 positive, or by unknown factors between DQ and DR and (e) DQB1*0602-DQA1*0102 confers protection in a dominant manner. This large study does not confirm the positive association previously observed in Norwegians between the DQ8/DQ4 genotype and IDDM, as this genotype was not significantly associated with IDDM in Swedish patients. The new findings in this study include (a) that DQ8/DQ6 (DQB1*0604-DQA1*0102) was associated with IDDM in Swedish patients and (b) analysis of individual amino acids in DQB1 chain does not fully explain susceptibility to IDDM.
authors.affiliation: Karolinska Institute, Department of Molecular Medicine, Stockholm.
authors.forename: C B
authors.initials: CB
authors.lastname: Sanjeevi
authors.forename: M
authors.initials: M
authors.lastname: Landin-Olsson
authors.forename: I
authors.initials: I
authors.lastname: Kockum
authors.forename: G
authors.initials: G
authors.lastname: Dahlquist
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility / Q000453:epidemiology / Q000276:immunology; D005799:Genes, Dominant; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D013548:Sweden / Q000453:epidemiology
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen