Genomic HLA-DQbeta Polymorphism Associated with Insulin-Dependent Diabetes Mellitus.

Abstract

Twelve insulin-dependent diabetes mellitus (IDDM) patients and healthy controls, who all carried the serologically defined DR3 and DR4 antigens, were compared with respect to other HLA polymorphisms. No significant differences between patients and controls were found by typing for HLA-Dw determinants by homozygous cell typing, nor by studies of their genomic DR.beta. polymorphism using different restriction enzymes. In contrast, certain DR4-associated genomic DQ.beta. fragments had a significantly different distribution among the IDDM patients than among the controls. Furthermore, when the distribution of all DQ.beta.-specific fragments which demonstrated polymorphism in our material was taken into account, nine of the 12 DR3, 4 IDDM patients demonstrated a similar DQ.beta. polymorphism compared with only two out of the 12 DR3, 4 controls (P = 0.006; corrected P = 0.037). Cells from patients and controls who demonstrated this IDDM-associated DQ.beta. polymorphism stimulated each other significantly less in reciprocal MLC tests, compared with the responses seen when their cells were confronted with cells from the DR3, 4 individuals with other genomic DQ.beta. polymorphisms.