title: The amino acid at position 57 of the HLA-DQ beta chain and susceptibility to develop insulin-dependent diabetes mellitus.
abstract: In Caucasoids HLA-DQB1 genes encoding amino acids other than aspartic acid at position 57 of the DQ beta chain (non-Asp-57) are associated with susceptibility to develop insulin-dependent diabetes mellitus (IDDM), while resistance is associated with aspartic acid at this residue (Asp-57). Following amplification of genomic DNA by the polymerase chain reaction, the DQB1 alleles of 87 random Norwegian IDDM patients and 187 healthy controls were investigated with 11 different sequence-specific oligonucleotide probes. Of these patients 82% carried DQB1 alleles encoding non-Asp-57 at both of their DQ beta chains, compared to 27% of the controls (relative risk = 12.2, p less than 0.0001). Sixteen percent of the patients (versus 51% of the controls) were heterozygous Asp-57/non-Asp-57. Two percent of the patients (22% of the controls) were apparently Asp-57 homozygous. The results demonstrate that non-Asp-57 DQ beta chains are associated with susceptibility to develop IDDM but also indicate that the protection associated with DQ beta Asp-57 may not be as dominant as reported by others.
authors.affiliation: Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
authors.forename: K S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: T
authors.initials: T
authors.lastname: Iwe
authors.forename: T S
authors.initials: TS
authors.lastname: Halstensen
authors.forename: A
authors.initials: A
authors.lastname: Spurkland
authors.forename: E
authors.initials: E
authors.lastname: Thorsby
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics*; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D004198:Disease Susceptibility; D004591:Electrophoresis, Polyacrylamide Gel; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D019914:Taq Polymerase
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D001224:Aspartic Acid; D019914:Taq Polymerase; D004259:DNA-Directed DNA Polymerase