High frequency of the HLA-DRB1*0405-(Dw15)-DQw8 haplotype in Spaniards and its relationship to diabetes susceptibility.
A study of DR4 subtypes has been done in Spanish unrelated controls and insulin-dependent diabetics by using dot blot hybridization with specific DR4B1 exon-2 oligonucleotides and automated dideoxy DNA sequencing. Dw15-DQw8 is the predominant DR4 subtype present in our normal population (37%); this DR4 frequency characteristic singles out our population from all other Caucasoids tested so far and may also be a marker of the original Iberian paleo-North African population. Dw15-DQw8 is not significantly increased in our insulin-dependent diabetics sample and despite its relative high frequency in the control population it does not have a bearing in lowering insulin-dependent diabetes mellitus frequency of DR4-positive Spaniards. In addition, no particular DR4 split is by itself significantly increased in Spanish diabetics; this may indicate that selective diabetogenic environmental factors may be working upon DR4-positive individuals, but on genes (or gene products) other than DR or at least not upon the polymorphic sites of DRB1 exon-2 products.
Morales
P
P
Department of Immunology, Hospital 12 de Octubre, Madrid, Spain.
Martinez-Laso
J
J
Martin-Villa
J M
JM
Corell
A
A
Vicario
J L
JL
Varela
P
P
Pérez-Aciego
P
P
Arnaiz-Villena
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010641:Phenotype; D016133:Polymerase Chain Reaction
D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes; D004247:DNA