The HLA class II-related susceptibility to type I insulin-dependent diabetes mellitus (IDDM) is examined in 94 multiplex families sorted by the presence or absence of a DR4+ haplotype in at least one diabetic family member. The families with DR4+ haplotypes are then sorted by the presence or absence of a DR4-linked DQβ3.2 allele. Further analysis assumes each multiplex family to represent a single diabetic genetic event and identifies the HLA class II haplotype(s) present in all affected members. The DQβ3.2 allele is present in over 95% of the multiplex families where DR4+ haplotypes segregate with IDDM, implying a major permissive role in determining susceptibility to IDDM.

References

Bertrams J, Baur M (1984): Insulin dependent diabetes mellitus. In E Albert, M Baur, W Mayr (eds): Histocompatibility Testing. Berlin: Springer-Verlag, pp 348–358.
10.1007/978-3-642-69770-8_118
Google Scholar
Holbeck SL, Nepom GT (1986): Exon-specific oligonucleotide probes localize HLA DQ beta allelic polymorphisms. Immunogenetics 24: 251–258.
10.1007/BF00364529
CAS PubMed Web of Science® Google Scholar
Kim S-J, Holbeck SL, Nisperos B, Hansen JA, Maeda H, Nepom GT (1985): Identification of a polymorphic variant associated with HLA-DQw3 and characterized by specific restriction sites within the DQ beta-chain gene. Proc Natl Acad Sci USA 82: 8139–8143.
10.1073/pnas.82.23.8139
CAS PubMed Web of Science® Google Scholar
Michelsen B, Lernmark A (1987): Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin dependent diabetes mellitus with HLA DQ. J Clin Invest 79: 1144–1152.
10.1172/JCI112931
CAS PubMed Web of Science® Google Scholar
Nepom BS, Nepom GT, Mickelson E, Antonelli P, Hansen JA (1983): Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: Correlation between beta-chain diversity and HLA-D. Proc Natl Acad Sci USA 80: 6962–6966.
10.1073/pnas.80.22.6962
CAS PubMed Web of Science® Google Scholar
Nepom GT, Palmer J, Nepom B (1986a): Specific HLA class II variants associated with IDDM. In MA Jaworski, GD Molnar, RV Rajotte, B Singh (eds) “ Immunology of Diabetes Mellitus.” Netherlands: Elsvier Publishers, pp 9–20.
Google Scholar
Nepom GT, Seyfried CE, Holbeck SL, Wilske KR, Nepom BS (1986b): Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis. Lancet ii (8514): 1002–1005.
10.1016/S0140-6736(86)92614-0
Google Scholar
Nepom BS, Palmer J, Kim S-J, Hansen JA, Holbeck SL, Nepom GT (1986c): Specific genomic markers for the HLA-DQ subregion discriminate between DR4+ insulin-dependent diabetes mellitus and DR4+ seropositive juvenile rheumatoid arthritis. J Exp Med 164: 345–350.
10.1084/jem.164.1.345
CAS PubMed Web of Science® Google Scholar
Reinsmoen N, Bach F (1982): Five HLA-D clusters associated with HLA-DR4. Hum Immunol 4: 249–258.
10.1016/0198-8859(82)90040-4
PubMed Web of Science® Google Scholar

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Volume6, Issue1

Special Issue:Genetic Analysis of Complex trait: Insulin‐Department Diabetes Mellitus and Affective Disorders

1989

Pages 149-154

HLA DQβ3.2 identifies subtypes of DR4 + haplotypes permissive for IDDM

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HLA DQβ3.2 identifies subtypes of DR4 + haplotypes permissive for IDDM

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