A Systematic Study of HLA Class II-β DNA Restriction Fragments in Insulin-Dependent Diabetes Mellitus

DNA restriction fragments of the genes encoding HLA class II-β antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), we...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1985-05, Vol.82 (10), p.3335-3339
Main Authors: Cohen-Haguenauer, Odile, Robbins, Elizabeth, Massart, Catherine, Busson, Marc, Deschamps, Ingeborg, Hors, Jacques, Lalouel, Jean-Marc, Dausset, Jean, Cohen, Daniel
Format: Article
Language:English
Subjects:
Antigens
Biological and medical sciences
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
DNA
DNA probes
DNA Restriction Enzymes
Enzymes
Fundamental and applied biological sciences. Psychology
Genes
Genes. Genome
Haplotypes
Histocompatibility Antigens Class II - genetics
HLA antigens
HLA-DR Antigens
Humans
Medical genetics
Molecular and cellular biology
Molecular genetics
Polymorphism, Genetic
Restriction fragment length polymorphism
Sodium
Statistics as Topic
Type 1 diabetes mellitus
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Summary:DNA restriction fragments of the genes encoding HLA class II-β antigens were compared in 34 patients with insulin-dependent diabetes mellitus and 34 HLA-DR-matched healthy individuals. Ninety-three fragments, determined by six restriction enzymes (EcoRI, EcoRV, HindIII, BamHI, Pvu II, and Taq I), were analyzed: (i) A DR Taq I 12.7-kilobase-pair fragment might be a marker for the extended haplotype HLA-B8,DR3. (ii) In controls, DR4 haplotypes are associated with two distinct clusters of DQ restriction fragments (DQR4 and DQR5). Almost all (94%) DR4 patients belong to the DQR4 and not to the DQR5 cluster. This suggests that, among HLA-DR4 haplotypes, only DQR4 haplotypes are involved in susceptibility to insulin-dependent diabetes mellitus. (iii) A DR Taq I 14.5-kilobase-pair fragment was found to be strongly associated with DQR4, mainly in DR3/DR4 heterozygous patients (P = 5 × 10-4). However, these results must be interpreted with caution, taking into account the high number of statistical tests performed.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.82.10.3335