HLA-DQB 1 codon 57 and genetic susceptibility to type 1 (insulin-dependent) diabetes mellitus in French children.

Variations in the incidence rate of Type 1 (insulin-dependent) diabetes mellitus might relate to ethnic-specific genetic backgrounds. HLA-DQB 1 alleles were typed in 75 French diabetic children and 85 matched control children. Enzymatically-amplified DQB 1 exon 2 was hybridized with oligoprobes specific for the six most common alleles. Alleles coding for an Asp residue at position 57 in the DQ beta chain are strongly negatively associated with Type 1 diabetes in the French population. Nevertheless, one of the diabetic children was an Asp 57 homozygote (DQB 1.2/3.1). Among alleles coding for a residue other than Asp at position 57, alleles 3.2 and 2 (Ala 57) are positively associated with diabetes but not allele 1.1 (Val 57) which is less frequent in diabetic children than in control children. Heterozygosity for 2/3.2 alleles is the genotype most strongly associated with diabetes (Odds ratio = 52.9). Large comparative population studies will be necessary to determine whether the frequency of DQB 1 alleles positively associated with Type 1 diabetes (2 and 3.2) in a given ethnicity is related to its incidence rate in the same population.