Heterogeneity of HLA genetic factors in IDDM susceptibility.
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 DR3/3 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.
Martell
M
M
Centre d'Etude du Polymorphisme Humain, Paris, France.
Marcadet
A
A
Moine
A
A
Boitard
C
C
Deschamps
I
I
Dausset
J
J
Bach
J F
JF
Cohen
D
D
D000483:Alleles; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012150:Polymorphism, Restriction Fragment Length
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes