Relationship between HLA-DQ and -DR genotypes and clinical characteristicsin a French population of Type 1 diabetic patients

Aims The present study was designed to look for a heterogeneity in the asso ciation between Type 1 diabetes mellitus (DM) and class II alleles of major histocompatibility complex (MHC) according to clinical presentation and C- peptide secretion during the first year of the disease, in a population liv ing in south of France. Methods HLA DRB1 and DQB1 genotypes were determined in 129 Caucasoid patien ts with Type 1 DM and compared to a control group (n = 88). In a subgroup o f 46 young adult diabetic patients, basal and postglucagon C-peptide secret ion was followed during the first year of the disease (at 0, 1, 3, 6, 9 and 12 months). Results The two main haplotypes associated with Type 1 DM were DRB1*04DQB1* 0302 and DRB1*03DQB1*02. The genotypes DRB1* 04DQB1*0302/DRB1*04DQB1*0302 a nd DRB1*03DQB1*02/DRB1*04DQB1* 0302 were associated with an early onset of diabetes, while homozygosity for DRB1*03DQB1*02 was characterized by later onset. Levels of residual insulin secretion in patients genotyped DRB1*03DQ A1*0501DQB1* 02/DRB1* 04DQA1*0301DQB1*0302 were higher than in patients gen otyped DRB1* 3DQA1*0501DQB1*02/DRB1*XDQA1*XDQB1*X or DRB1* XDQA1* XDQB1*X/D RB1*XDQA1*XDQB1*X. Conclusions This study confirms some clinical heterogeneity of Type 1 DM li nked to HLA DR and DQ genotypes, and leads to a paradoxical finding: DQB1*0 2/DQB1*0302 combination predisposes to an early onset in the whole populati on but residual secretion of insulin disappears more slowly in a subgroup o f young adults with recently diagnosed diabetes. These data suggest that in terrelations between MHC genotype and diabetogenic process could be differe nt at various ages of life.