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Heterogeneity of HLA genetic factors in IDDM susceptibility
Authors:M Martell  A Marcadet  A Moine  C Boitard  I Deschamps  J Dausset  J F Bach  D Cohen
Institution:(1) Centre d'Etude du Polymorphisme Humain (CEPH), 27, Rue Juliette Dodu, F-75010 Paris, France;(2) Centre de Transfusion Sanguine de la Savoie, 502, Fg Maché, BP1125, F-73011 Chamberry, France;(3) INSERM U25, Hôpital Necker, 161, Rue de Sevres, F-75015 Paris, France;(4) INSERM U30, Hôpital Necker Enfants Malades, 149, Rue de Sevres, F-75015 Paris, France
Abstract:The association of certain HLA-D alleles with insulin-dependent diabetes mellitus (IDDM) is well known. One hundred and sixty-one non-related diabetic individuals and 142 non-related healthy controls were typed for the HLA DR-DQw-Dw association, using a restriction fragment length polymorphism (RFLP) typing method that combines three probe/enzyme systems: DRB/Taq I, DQB/Taq I, and DQB/Bam HI. Comparison of frequencies in both diabetics and controls confirms previous results in terms of HLA class II and IDDM association. Moreover, we have found that DR3/4 heterozygous individuals are more susceptible to IDDM when they are also Dw25 (associated with B18) than when they are Dw24 (associated with B8). Using oligonucleotide dot-blot hybridizations we analyzed the HLA-DQB1 sequence of DR3, Dw24 and DR3, Dw25 homozygous individuals, and we found no difference at position 57 between these two DR3-carrying haplotypes. This observation points to the heterogeneity of HLA genetic factors in IDDM susceptibility. Offprint requests to: D. Cohen.
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