Comparison between HLA-DRB and DQ DNA sequences and classic serological markers as Type 11 (insulin-dependent)diabetes mellitus predictive risk markers in the Spanish population

Autor: Oscar G. Segurado, P. Morales, Jorge Martinez-Laso, José Manuel Martín-Villa, Alfredo Corell, Antonio Arnaiz-Villena, D De Juan, Jose L. Vicario, Gregorio Lledo
Rok vydání: 1992
Předmět:
Zdroj: Diabetologia. 35:475-481
ISSN: 1432-0428
0012-186X
DOI: 10.1007/bf02342447
Popis: The question of HLA susceptibility to Type 1(insulin-dependent) diabetes mellitus remains unresolved. In the present study, 127 diabetic patients and 177 unrelated control subjects have been analysed for their class I and class II serological antigens, class II (DR, DQ) DNA restriction fragment length polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding amino acid residues. By using the aetiologic fraction (δ) as an almost absolute measure of the strongest linkage disequilibrium of an HLA marker to the putative Type 1 diabetes susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DR4 < DR3 < DR3 or DR4 < non-Aspartate 57 sDQ and Arginine 52 αDQ < Arginine 52 αDQ. Thus, molecular HLA-DQ markers appear to be more accurate as susceptibility markers than the classic serologically defined ones (DR3 and DR4); however, any effect of DQ markers disapears when non-DR3/DR4 individuals are considered, suggesting that DR factors (or others in between DQ and DR) are also important. In addition, a dominant non-Aspartate 57 sDQ susceptibility theory does not hold (but a recessive one does) in our diabetic population (probably due to the high frequency of the protective DR7-non-Aspartate 57 sDQ haplotypes); Arginine 52 aDQ is the best single HLA marker found in our population, both as a recessive or as a dominant one. Also there are 13 patients in our sample who bear neither Arginine 52 aDQ nor non-Aspartate 57 sDQ susceptibility factors. On the other hand, a predominant Type 1 diabetes association of Spanish patients to the B18-DR3-Dw25 haplotype (and not to B8-DR3-Dw24) has been found; this distinctive association has also been recorded in adult systemic lupus patients and may reflect the existence of common pathogenetic HLA factors for both diseases present only in the B18-DR3-Dw25 haplotype in the Spanish population. These factors are probably placed at the non-coding regions which are different from the B8-DR3-Dw24 haplotype.
Databáze: OpenAIRE
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